VCV000012138.9 - ClinVar

NM_000387.6(SLC25A20):c.713A>G (p.Gln238Arg)

Germline

Classification

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

Pathogenic
Pathogenic (4)

4 out of 5 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.713A>G (p.Gln238Arg)

Variation ID: 12138 Accession: VCV000012138.9

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3p21.31 3: 48859097 (GRCh38) [ NCBI UCSC ] 3: 48896530 (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	Apr 13, 2025	Oct 9, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000387.6:c.713A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000378.1:p.Gln238Arg	missense
NC_000003.12:g.48859097T>C
NC_000003.11:g.48896530T>C
NG_008171.1:g.44800A>G
	O43772:p.Gln238Arg

... more HGVS ... less HGVS

Protein change

Q238R

Other names

Canonical SPDI

NC_000003.12:48859096:T: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.

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

Links

ClinGen: CA121918 UniProtKB: O43772#VAR_021820 OMIM: 613698.0007 dbSNP: rs28934589 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 (4)	criteria provided, multiple submitters, no conflicts	Oct 9, 2024	RCV000012921.17
not provided	Pathogenic (1)	criteria provided, single submitter	Dec 17, 2013	RCV000153966.15

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 (Apr 04, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Carnitine acylcarnitine translocase deficiency	Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre Accession: SCV004810053.1 First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024	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 17, 2013) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015)	not provided	Eurofins Ntd Llc (ga) Accession: SCV000203586.8 First in ClinVar: Feb 02, 2015 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SLC25A20 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: 2 Zygosity: 2 Homozygotes Sex: mixed

Pathogenic (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Carnitine acylcarnitine translocase deficiency	Pathology and Clinical Laboratory Medicine, King Fahad Medical City Accession: SCV000996281.1 First in ClinVar: Oct 19, 2019 Last updated: Oct 19, 2019	Comment: show Compatible metabolite assay (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 Number of individuals with the variant: 2 Ethnicity/Population group: Arab Geographic origin: Middle East

Pathogenic (Oct 09, 2024) 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: SCV005422514.1 First in ClinVar: Dec 14, 2024 Last updated: Dec 14, 2024	Publications: PubMed (3) PubMed: 12859414‚ 15057979‚ 15159657 Comment: show Variant summary: SLC25A20 c.713A>G (p.Gln238Arg) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250762 control chromosomes. c.713A>G has been reported in the literature in multiple individuals affected with Carnitine-Acylcarnitine Translocase Deficiency (e.g. Al Aqeel_2003, Galron_2004, Iacobazzi_2004). These data indicate that the variant is very likely to be associated with disease. Additionally, at least two publications report that the variant results in enzyme activities <5% of normal in fibroblasts from homozygous patients (e.g. Al Aqeel_2003, Iacobazzi_2004). The following publications have been ascertained in the context of this evaluation (PMID: 12859414, 15159657, 15057979). ClinVar contains an entry for this variant (Variation ID: 12138). Based on the evidence outlined above, the variant was 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 (Apr 15, 2004) N Not contributing to aggregate classification	no assertion criteria provided	CARNITINE-ACYLCARNITINE TRANSLOCASE DEFICIENCY	OMIM Accession: SCV000033162.3 First in ClinVar: Apr 04, 2013 Last updated: Aug 09, 2019	Publications: PubMed (2) PubMed: 12859414‚ 15057979 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 Saudi patient with virtually complete CACT deficiency (CACTD; 212138) in fibroblasts, born to first-cousin parents, Al Aqeel et al. (2003) identified homozygosity for … (more) In a Saudi patient with virtually complete CACT deficiency (CACTD; 212138) in fibroblasts, born to first-cousin parents, Al Aqeel et al. (2003) identified homozygosity for a 712A-G transition in the cDNA of the SLC25A20 gene, resulting in a glu238-to-arg (Q238R) substitution. The patient presented on the second day of life with nystagmus and hyperammonemia. Thickened interventricular septum of the heart was demonstrated. The patient died at 7 months of age as a result of cardiac arrhythmia; 3 sibs had previously died as neonates. In an Arab male infant with CACT deficiency, Iacobazzi et al. (2004) demonstrated homozygosity for the Q238R mutation in the SLC25A20 gene. The proband was the third child of consanguineous parents. Their second child, a female, died in Saudi Arabia at 3 days of age with an illness similar to the one in the proband. (less)

Comment:

Variant summary: SLC25A20 c.713A>G (p.Gln238Arg) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250762 control chromosomes. c.713A>G has been reported in the literature in multiple individuals affected with Carnitine-Acylcarnitine Translocase Deficiency (e.g. Al Aqeel_2003, Galron_2004, Iacobazzi_2004). These data indicate that the variant is very likely to be associated with disease. Additionally, at least two publications report that the variant results in enzyme activities <5% of normal in fibroblasts from homozygous patients (e.g. Al Aqeel_2003, Iacobazzi_2004). The following publications have been ascertained in the context of this evaluation (PMID: 12859414, 15159657, 15057979). ClinVar contains an entry for this variant (Variation ID: 12138). Based on the evidence outlined above, the variant was classified as pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Carnitine-acylcarnitine translocase deficiency: identification of a novel molecular defect in a Bedouin patient.	Galron D	Journal of inherited metabolic disease	2004	PMID: 15159657
Response to therapy in carnitine/acylcarnitine translocase (CACT) deficiency due to a novel missense mutation.	Iacobazzi V	American journal of medical genetics. Part A	2004	PMID: 15057979
A novel molecular defect of the carnitine acylcarnitine translocase gene in a Saudi patient.	Al Aqeel AI	Clinical genetics	2003	PMID: 12859414
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SLC25A20	-	-	-	-

Text-mined citations for rs28934589 ...

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 Jul 15, 2026