VCV000012137.25 - ClinVar

NM_000387.6(SLC25A20):c.199-10T>G

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (10)

10 out of 12 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000387.6(SLC25A20):c.199-10T>G

Variation ID: 12137 Accession: VCV000012137.25

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3p21.31 3: 48884134 (GRCh38) [ NCBI UCSC ] 3: 48921567 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 27, 2014	Mar 7, 2026	Jan 13, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_000387.6:c.199-10T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NC_000003.12:g.48884134A>C
NC_000003.11:g.48921567A>C
NG_008171.1:g.19763T>G

Protein change

Other names

p.?
IVS2AS, T-G, -10

Canonical SPDI

NC_000003.12:48884133:A:C

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00020 (C)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00002

The Genome Aggregation Database (gnomAD), exomes 0.00002

Exome Aggregation Consortium (ExAC) 0.00003

The Genome Aggregation Database (gnomAD) 0.00003

Trans-Omics for Precision Medicine (TOPMed) 0.00003

The Genome Aggregation Database (gnomAD), exomes 0.00007

1000 Genomes Project 30x 0.00016

1000 Genomes Project 0.00020

Links

ClinGen: CA121917 OMIM: 613698.0006 dbSNP: rs541208710 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
SLC25A20		-	-	GRCh38 GRCh37	362	378

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Carnitine acylcarnitine translocase deficiency	Pathogenic (9)	criteria provided, multiple submitters, no conflicts	Jan 13, 2026	RCV000012920.25
not provided	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Mar 21, 2025	RCV000427395.6
SLC25A20-related disorder	Pathogenic (1)	no assertion criteria provided	Jul 23, 2024	RCV004757104.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Mar 22, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Carnitine acylcarnitine translocase deficiency	Fulgent Genetics, Fulgent Genetics Accession: SCV005660679.1 First in ClinVar: Jan 25, 2025 Last updated: Jan 25, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Jan 06, 2017) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Carnitine acylcarnitine translocase deficiency	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000696660.1 First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017	Publications: PubMed (5) PubMed: 11592821‚ 12559850‚ 17277394‚ 25459972‚ 27066551 Comment: show Variant summary: The SLC25A20 c.199-10T>G variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a disease-causing outcome for this variant. 5/5 splice prediction tools predict the creation or enhancement of a cryptic splice donor site along with the weakening of a canonical splicing acceptor site. Functional studies have shown the patients with this variant in compound heterozygosity had exon 3/4 skipping, and abberant splicing was also observed in patients and parents who had coding variants suggesting coding sequence mutations might contribute to the presence of aberrantly spliced mRNA (Hsu_2001). The variant was found in numerous affected individuals both in the homozygous and heterozygous state, and the variant has been suggested as an Asian founder mutation. This variant was found in 4/121236 control chromosomes at a frequency of 0.000033, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC25A20 variant (0.001118). In addition, one reputable clinical diagnostic laboratory/multiple reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Nov 18, 2021) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV000515900.6 First in ClinVar: Mar 08, 2017 Last updated: Mar 04, 2023	Comment: show Reverse transcriptase PCR in patient fibroblasts indicate c.199-10 T>G results in abnormal gene splicing (Ogawa et al., 2000); This variant is associated with the following publications: (PMID: 25459972, 29137068, 10697964, 15363639, 11592821, 29996190, 31108048, 31965297, 31501239, 32411386, 33634872, 33194920, 32778825, 24088670) (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (Mar 13, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Carnitine acylcarnitine translocase deficiency	3billion Accession: SCV006584423.1 First in ClinVar: Oct 25, 2025 Last updated: Oct 25, 2025	Publications: PubMed (2) PubMed: 10697964‚ 11592821 Comment: show The variant is observed at an extremely low frequency in the gnomAD v4.1.0 dataset (total allele frequency: 0.003%). Predicted Consequence/Location: Intron variant: previously reported to alter splicing and result in a loss of normal protein function through nonsense-mediated decay (NMD) or protein truncation (PMID: 10697964, 11592821). In silico tools predict the variant to alter splicing and produce an abnormal transcript [SpliceAI: 0.65 (spliceogenicity >=0.2, non-spliceogenicity <0.1)]. The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 10697964, 11592821). The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000012137 / PMID: 10697964 / 3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Method: exome sequencing

Pathogenic (Mar 21, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV007137319.1 First in ClinVar: Jan 11, 2026 Last updated: Jan 11, 2026	Publications: PubMed (6) PubMed: 11592821‚ 12559850‚ 21605995‚ 24088670‚ 25459972‚ 31108048 Comment: show PP4, PM2_supporting, PM3_very_strong, PS4 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 1

Pathogenic (May 10, 2019) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Carnitine acylcarnitine translocase deficiency	Center for Molecular Medicine, Children’s Hospital of Fudan University Accession: SCV001190562.1 First in ClinVar: Mar 29, 2020 Last updated: Mar 29, 2020	Observation: 1 Collection method: clinical testing Allele origin: paternal Affected status: yes Observation 1 Collection method: clinical testing Allele origin: paternal Affected status: yes

Pathogenic (Mar 26, 2020) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Carnitine acylcarnitine translocase deficiency (Autosomal recessive inheritance)	Genetics and Molecular Pathology, SA Pathology Accession: SCV002556627.2 First in ClinVar: Aug 04, 2022 Last updated: Dec 17, 2022	Publications: PubMed (2) PubMed: 10697964‚ 25459972 Comment: show The SLC25A20:c.199-10T>G variant is a single nucleotide substitution which results in aberrant splicing. The variant has been reported in the literature as homozygous or heterozygous in combination with another SLC25A20 variant in affected patients (PMID: 25459972, PMID: 25459972) . It has been described as a founder mutation in East Asian populations. RNA studies demonstrate exon 3 and exon 3/4 skipping which is predicted to be detrimental to protein function (PMID: 10697964). It is present in population databases at 0.007% (20 het/280674 allele count) (PP). Splice prediction programs in Alamut indicate that the variant may disrupt the exon 3 acceptor site. The variant is described in ClinVar as pathogenic and HGMD (2019.4) as disease causing (PP5). (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (Mar 27, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Carnitine acylcarnitine translocase deficiency	Baylor Genetics Accession: SCV004201707.2 First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Pathogenic (Mar 04, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Carnitine acylcarnitine translocase deficiency (Autosomal recessive inheritance)	Institute of Human Genetics, University of Leipzig Medical Center Accession: SCV005900186.2 First in ClinVar: Mar 29, 2025 Last updated: Apr 13, 2025	Comment: show Criteria applied: PM2,PM3,PP4,PVS1 (less) Observation: 1 Collection method: clinical testing Allele origin: maternal Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: maternal Affected status: yes Clinical Features: Seizure (present) , Glutaric aciduria (present) , Hypoglycemia (present) Sex: female

Pathogenic (Jan 13, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Carnitine acylcarnitine translocase deficiency	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000632619.8 First in ClinVar: Dec 26, 2017 Last updated: Mar 07, 2026	Publications: PubMed (5) PubMed: 10697964‚ 24088670‚ 25459972‚ 26238931‚ 27066551 Comment: show This sequence change falls in intron 2 of the SLC25A20 gene. It does not directly change the encoded amino acid sequence of the SLC25A20 protein. This variant is present in population databases (rs541208710, gnomAD 0.09%). This variant has been observed in individuals with carnitine–acylcarnitine translocase deficiency (PMID: 10697964, 24088670, 25459972, 26238931, 27066551). It has also been observed to segregate with disease in related individuals. This variant is also known as 261-10T>G. ClinVar contains an entry for this variant (Variation ID: 12137). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Jul 23, 2024) N Not contributing to aggregate classification	no assertion criteria provided	SLC25A20-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV005358930.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: show The SLC25A20 c.199-10T>G variant is predicted to interfere with splicing. This variant has been reported in the compound heterozygous and homozygous state in multiple patients with autosomal recessive carnitine-acylcarnitine translocase deficiency (Ogawa et al. 2000. PubMed ID: 10697964, Tang et al. 2019. PubMed ID: 31108048, Vatanavicharn et al. 2015. PubMed ID: 25459972). RNA studies showed that this variant leads to aberrant splicing and truncation of the protein (Ogawa et al. 2000. PubMed ID: 10697964). This variant is reported in 0.095% of alleles in individuals of East Asian descent in gnomAD. This variant is interpreted as pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Dec 01, 2013) N Not contributing to aggregate classification	no assertion criteria provided	CARNITINE-ACYLCARNITINE TRANSLOCASE DEFICIENCY	OMIM Accession: SCV000033161.3 First in ClinVar: Apr 04, 2013 Last updated: Aug 09, 2019	Publications: PubMed (2) PubMed: 10697964‚ 24088670 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: In a patient with CACT deficiency (CACTD; 212138), Ogawa et al. (2000) found compound heterozygosity for a splice site mutation, a T-to-G transversion at the … (more) In a patient with CACT deficiency (CACTD; 212138), Ogawa et al. (2000) found compound heterozygosity for a splice site mutation, a T-to-G transversion at the nucleotide -10 upstream from the splice acceptor site of intron 2, and a 146delT mutation (613698.0005). In a Japanese patient who died of CACT deficiency, Fukushima et al. (2013) identified compound heterozygous mutations in the SLC25A20 gene: a T-to-G transversion in intron 2 (c.199-10T-G) and W192X (613698.0008). Each unaffected parent was heterozygous for 1 of the mutations. (less)

Comment:

Variant summary: The SLC25A20 c.199-10T>G variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a disease-causing outcome for this variant. 5/5 splice prediction tools predict the creation or enhancement of a cryptic splice donor site along with the weakening of a canonical splicing acceptor site. Functional studies have shown the patients with this variant in compound heterozygosity had exon 3/4 skipping, and abberant splicing was also observed in patients and parents who had coding variants suggesting coding sequence mutations might contribute to the presence of aberrantly spliced mRNA (Hsu_2001). The variant was found in numerous affected individuals both in the homozygous and heterozygous state, and the variant has been suggested as an Asian founder mutation. This variant was found in 4/121236 control chromosomes at a frequency of 0.000033, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC25A20 variant (0.001118). In addition, one reputable clinical diagnostic laboratory/multiple reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.

Comment:

Reverse transcriptase PCR in patient fibroblasts indicate c.199-10 T>G results in abnormal gene splicing (Ogawa et al., 2000); This variant is associated with the following publications: (PMID: 25459972, 29137068, 10697964, 15363639, 11592821, 29996190, 31108048, 31965297, 31501239, 32411386, 33634872, 33194920, 32778825, 24088670)

Comment:

The variant is observed at an extremely low frequency in the gnomAD v4.1.0 dataset (total allele frequency: 0.003%). Predicted Consequence/Location: Intron variant: previously reported to alter splicing and result in a loss of normal protein function through nonsense-mediated decay (NMD) or protein truncation (PMID: 10697964, 11592821). In silico tools predict the variant to alter splicing and produce an abnormal transcript [SpliceAI: 0.65 (spliceogenicity >=0.2, non-spliceogenicity <0.1)]. The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 10697964, 11592821). The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000012137 / PMID: 10697964 / 3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

Comment:

The SLC25A20:c.199-10T>G variant is a single nucleotide substitution which results in aberrant splicing. The variant has been reported in the literature as homozygous or heterozygous in combination with another SLC25A20 variant in affected patients (PMID: 25459972, PMID: 25459972) . It has been described as a founder mutation in East Asian populations. RNA studies demonstrate exon 3 and exon 3/4 skipping which is predicted to be detrimental to protein function (PMID: 10697964). It is present in population databases at 0.007% (20 het/280674 allele count) (PP). Splice prediction programs in Alamut indicate that the variant may disrupt the exon 3 acceptor site. The variant is described in ClinVar as pathogenic and HGMD (2019.4) as disease causing (PP5).

Comment:

This sequence change falls in intron 2 of the SLC25A20 gene. It does not directly change the encoded amino acid sequence of the SLC25A20 protein. This variant is present in population databases (rs541208710, gnomAD 0.09%). This variant has been observed in individuals with carnitine–acylcarnitine translocase deficiency (PMID: 10697964, 24088670, 25459972, 26238931, 27066551). It has also been observed to segregate with disease in related individuals. This variant is also known as 261-10T>G. ClinVar contains an entry for this variant (Variation ID: 12137). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

Comment:

The SLC25A20 c.199-10T>G variant is predicted to interfere with splicing. This variant has been reported in the compound heterozygous and homozygous state in multiple patients with autosomal recessive carnitine-acylcarnitine translocase deficiency (Ogawa et al. 2000. PubMed ID: 10697964, Tang et al. 2019. PubMed ID: 31108048, Vatanavicharn et al. 2015. PubMed ID: 25459972). RNA studies showed that this variant leads to aberrant splicing and truncation of the protein (Ogawa et al. 2000. PubMed ID: 10697964). This variant is reported in 0.095% of alleles in individuals of East Asian descent in gnomAD. This variant is interpreted as pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Clinical and molecular characteristics of carnitine-acylcarnitine translocase deficiency: Experience with six patients in Guangdong China.	Tang C	Clinica chimica acta; international journal of clinical chemistry	2019	PMID: 31108048
Expanding genotype/phenotype of neuromuscular diseases by comprehensive target capture/NGS.	Tian X	Neurology. Genetics	2015	PMID: 27066551
SSIEM 2015 Annual Symposium : Lyon, France, August 2015.	-	Journal of inherited metabolic disease	2015	PMID: 26238931
Carnitine-acylcarnitine translocase deficiency: Two neonatal cases with common splicing mutation and in vitro bezafibrate response.	Vatanavicharn N	Brain & development	2015	PMID: 25459972
Three novel mutations in the carnitine-acylcarnitine translocase (CACT) gene in patients with CACT deficiency and in healthy individuals.	Fukushima T	Journal of human genetics	2013	PMID: 24088670
Expanded molecular features of carnitine acyl-carnitine translocase (CACT) deficiency by comprehensive molecular analysis.	Wang GL	Molecular genetics and metabolism	2011	PMID: 21605995
Carnitine-acylcarnitine translocase deficiency in three neonates presenting with rapid deterioration and cardiac arrest.	Lee RS	Hong Kong medical journal = Xianggang yi xue za zhi	2007	PMID: 17277394
Mutational spectrum and DNA-based prenatal diagnosis in carnitine-acylcarnitine translocase deficiency.	Costa C	Molecular genetics and metabolism	2003	PMID: 12559850
Aberrant mRNA splicing associated with coding region mutations in children with carnitine-acylcarnitine translocase deficiency.	Hsu BY	Molecular genetics and metabolism	2001	PMID: 11592821
Identification of two novel mutations of the carnitine/acylcarnitine translocase (CACT) gene in a patient with CACT deficiency.	Ogawa A	Journal of human genetics	2000	PMID: 10697964

Text-mined citations for rs541208710 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 13, 2026