VCV000025355.78 - ClinVar

NM_003060.4(SLC22A5):c.95A>G (p.Asn32Ser)

Germline

Classification

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

Pathogenic
Pathogenic (12)

12 out of 15 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_003060.4(SLC22A5):c.95A>G (p.Asn32Ser)

Variation ID: 25355 Accession: VCV000025355.78

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q31.1 5: 132370067 (GRCh38) [ NCBI UCSC ] 5: 131705759 (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	May 23, 2014	Jun 20, 2026	Jan 11, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_003060.4:c.95A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003051.1:p.Asn32Ser	missense
NM_001308122.2:c.95A>G	NP_001295051.1:p.Asn32Ser	missense
NC_000005.10:g.132370067A>G
NC_000005.9:g.131705759A>G
NG_008982.2:g.5364A>G
	O76082:p.Asn32Ser

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000005.10:132370066:A:G

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.

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) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00001

Links

ClinGen: CA342615 UniProtKB: O76082#VAR_064112 dbSNP: rs72552725 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.
SLC22A5		-	-	GRCh38 GRCh37	1327	1372

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.
Renal carnitine transport defect	Pathogenic (7)	criteria provided, multiple submitters, no conflicts	Jan 11, 2026	RCV000022302.30
not provided	Pathogenic (5)	criteria provided, multiple submitters, no conflicts	Aug 25, 2021	RCV000414281.44
not specified	Pathogenic (1)	criteria provided, single submitter	Dec 29, 2016	RCV000506183.9
Inborn errors of metabolism	Pathogenic (1)	criteria provided, single submitter	Oct 28, 2025	RCV006694012.1
Carnitine deficiency	Pathogenic (1)	criteria provided, single submitter	Mar 20, 2025	RCV006638688.1

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 (Feb 23, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Renal carnitine transport defect	Baylor Genetics Accession: SCV004201261.2 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 (Apr 17, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Renal carnitine transport defect	Fulgent Genetics, Fulgent Genetics Accession: SCV002802071.2 First in ClinVar: Dec 31, 2022 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 (Oct 28, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACGS Best Practice Guidelines for Variant Classification in Rare Disease 2024)	Inborn error of metabolism	North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust Accession: SCV007592259.1 First in ClinVar: May 09, 2026 Last updated: May 09, 2026	Comment: show PM3_Str PM2_Mod PP4_Str (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 (Dec 29, 2016) C Contributing to aggregate classification	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	not specified	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000605132.1 First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017	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 15, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Renal carnitine transport defect	Genome-Nilou Lab Accession: SCV002055791.1 First in ClinVar: Jan 12, 2022 Last updated: Jan 12, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Pathogenic (Mar 03, 2017) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015)	not provided	Eurofins Ntd Llc (ga) Accession: SCV000700441.3 First in ClinVar: May 23, 2014 Last updated: Apr 13, 2025	Publications: PubMed (5) PubMed: 12210323‚ 17126586‚ 21922592‚ 25665836‚ 25846890 Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SLC22A5 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 Zygosity: 1 Single Heterozygote Sex: mixed

Pathogenic (May 16, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Renal carnitine transport defect	Revvity Omics, Revvity Accession: SCV002020651.4 First in ClinVar: Nov 29, 2021 Last updated: Sep 06, 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 11, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Renal carnitine transport defect	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000829202.8 First in ClinVar: Oct 10, 2018 Last updated: Feb 15, 2026	Publications: PubMed (5) PubMed: 12210323‚ 23653224‚ 23963628‚ 25665836‚ 28492532 Comment: show This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 32 of the SLC22A5 protein (p.Asn32Ser). This variant is present in population databases (rs72552725, gnomAD 0.01%). This missense change has been observed in individual(s) with primary carnitine deficiency (PMID: 12210323, 23653224, 23963628, 25665836). ClinVar contains an entry for this variant (Variation ID: 25355). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SLC22A5 protein function with a positive predictive value of 95%. 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 (May 22, 2017) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Renal carnitine transport defect	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000698159.1 First in ClinVar: May 23, 2014 Last updated: May 23, 2014	Publications: PubMed (1) PubMed: 27896095 Comment: show Variant summary: The SLC22A5 c.95A>G (p.Asn32Ser) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 3/112066 control chromosomes at a frequency of 0.0000268, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC22A5 variant (0.0045644). The variant has been reported in numerous affected individuals in the literature in the homozygous and compound heterozygous state. Additionally, carnitine uptake studies in cultured skin fibroblasts showed that the mean residual OCTN2 transporter activity was 4% of normal in patients homozygous for this variant (Rasmussen_2014). Multiple clinical diagnostic laboratories/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 (Aug 25, 2021) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV000490803.4 First in ClinVar: Jan 09, 2017 Last updated: Mar 04, 2023	Comment: show Published functional studies demonstrate carnitine transport activity was significantly impaired compared to controls (Rose et al., 2012); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25846890, 12210323, 21922592, 28841266, 31373028, 30219858, 30863740, 28105570, 28170084, 17126586, 23379544, 26828774, no PMID, 25665836, 23653224, 23963628) (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 20, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Natera Variant Classification Schema (03/2026))	Carnitine deficiency	Natera, Inc. Accession: SCV001458681.2 First in ClinVar: Jan 02, 2021 Last updated: Apr 04, 2026	Publications: PubMed (3) PubMed: 12210323‚ 22566287‚ 27896095 Comment: show The c.95A>G variant in SLC22A5 is a missense variant predicted to cause substitution of asparagine to serine at amino acid 32. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 12210323, 22566287, 27896095). Additionally, this variant has been observed to segregate in affected family members (PMID: 22566287). Given the available evidence, 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 (Mar 01, 2017) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV001245742.38 First in ClinVar: May 09, 2020 Last updated: Jun 20, 2026	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: 1

Pathogenic (May 18, 2017) N Not contributing to aggregate classification	no assertion criteria provided	Renal carnitine transport defect	Counsyl Accession: SCV000788592.3 First in ClinVar: Aug 04, 2018 Last updated: Jun 29, 2025	Publications: PubMed (2) PubMed: 23653224‚ 25846890 Comment: show This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. (less) 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 (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Study: VKGL Data-share Consensus Accession: SCV001800772.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021	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 (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Genome Diagnostics Laboratory, University Medical Center Utrecht Study: VKGL Data-share Consensus Accession: SCV001928024.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Comment:

This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 32 of the SLC22A5 protein (p.Asn32Ser). This variant is present in population databases (rs72552725, gnomAD 0.01%). This missense change has been observed in individual(s) with primary carnitine deficiency (PMID: 12210323, 23653224, 23963628, 25665836). ClinVar contains an entry for this variant (Variation ID: 25355). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SLC22A5 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

Comment:

Variant summary: The SLC22A5 c.95A>G (p.Asn32Ser) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 3/112066 control chromosomes at a frequency of 0.0000268, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC22A5 variant (0.0045644). The variant has been reported in numerous affected individuals in the literature in the homozygous and compound heterozygous state. Additionally, carnitine uptake studies in cultured skin fibroblasts showed that the mean residual OCTN2 transporter activity was 4% of normal in patients homozygous for this variant (Rasmussen_2014). Multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.

Comment:

Published functional studies demonstrate carnitine transport activity was significantly impaired compared to controls (Rose et al., 2012); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25846890, 12210323, 21922592, 28841266, 31373028, 30219858, 30863740, 28105570, 28170084, 17126586, 23379544, 26828774, no PMID, 25665836, 23653224, 23963628)

Comment:

The c.95A>G variant in SLC22A5 is a missense variant predicted to cause substitution of asparagine to serine at amino acid 32. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 12210323, 22566287, 27896095). Additionally, this variant has been observed to segregate in affected family members (PMID: 22566287). Given the available evidence, this variant is classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Importance of molecular diagnosis in the accurate diagnosis of systemic carnitine deficiency.	Hitomi T	Journal of genetics	2015	PMID: 25846890
Carnitine levels in skeletal muscle, blood, and urine in patients with primary carnitine deficiency during intermission of L-carnitine supplementation.	Rasmussen J	JIMD reports	2015	PMID: 25665836
Residual OCTN2 transporter activity, carnitine levels and symptoms correlate in patients with primary carnitine deficiency.	Rasmussen J	Molecular genetics and metabolism reports	2014	PMID: 27896095
Primary Carnitine deficiency in the Faroe Islands: health and cardiac status in 76 adult patients diagnosed by screening.	Rasmussen J	Journal of inherited metabolic disease	2014	PMID: 23963628
Carnitine levels in 26,462 individuals from the nationwide screening program for primary carnitine deficiency in the Faroe Islands.	Rasmussen J	Journal of inherited metabolic disease	2014	PMID: 23653224
Primary carnitine deficiency and pivalic acid exposure causing encephalopathy and fatal cardiac events.	Rasmussen J	Journal of inherited metabolic disease	2013	PMID: 22566287
Genotype-phenotype correlation in primary carnitine deficiency.	Rose EC	Human mutation	2012	PMID: 21922592
Expanded newborn screening identifies maternal primary carnitine deficiency.	Schimmenti LA	Molecular genetics and metabolism	2007	PMID: 17126586
Novel OCTN2 mutations: no genotype-phenotype correlations: early carnitine therapy prevents cardiomyopathy.	Lamhonwah AM	American journal of medical genetics	2002	PMID: 12210323
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SLC22A5	-	-	-	-

Text-mined citations for rs72552725 ...

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 Jun 20, 2026