VCV000947886.13 - ClinVar

NM_003060.4(SLC22A5):c.470C>T (p.Ser157Phe)

Germline

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.

(4)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Pathogenic(1); Uncertain significance(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_003060.4(SLC22A5):c.470C>T (p.Ser157Phe)

Variation ID: 947886 Accession: VCV000947886.13

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q31.1 5: 132378454 (GRCh38) [ NCBI UCSC ] 5: 131714146 (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	Jul 16, 2020	Nov 24, 2024	Sep 15, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_003060.4:c.470C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003051.1:p.Ser157Phe	missense
NM_001308122.2:c.542C>T	NP_001295051.1:p.Ser181Phe	missense
NC_000005.10:g.132378454C>T
NC_000005.9:g.131714146C>T
NG_008982.2:g.13751C>T

... more HGVS ... less HGVS

Protein change

S157F, S181F

Other names

p.Ser157Phe

Canonical SPDI

NC_000005.10:132378453:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

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), exomes 0.00000

Exome Aggregation Consortium (ExAC) 0.00001

Links

dbSNP: rs759925126 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	1174	1217

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.
Decreased circulating carnitine concentration	Uncertain significance (1)	no assertion criteria provided	Jul 6, 2020	RCV002226520.9
Renal carnitine transport defect	Pathogenic (2)	criteria provided, single submitter	Sep 15, 2023	RCV001219034.17
not provided	Uncertain significance (1)	criteria provided, single submitter	Sep 12, 2023	RCV004792811.1

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.	More information 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 (Sep 15, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Renal carnitine transport defect Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001390954.5 First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024	Publications: PubMed (1) PubMed: 35095998 Comment: This variant is present in population databases (rs759925126, gnomAD 0.0009%). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence … (more) This variant is present in population databases (rs759925126, gnomAD 0.0009%). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC22A5 protein function. ClinVar contains an entry for this variant (Variation ID: 947886). This missense change has been observed in individual(s) with clinical features of SLC22A5-related conditions (PMID: 35095998; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 157 of the SLC22A5 protein (p.Ser157Phe). (less)
Uncertain significance (Sep 12, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: unknown Allele origin: germline	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV005411862.1 First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024	Publications: PubMed (1) PubMed: 35095998 Comment: PP3, PM2, PM3_supporting Number of individuals with the variant: 1
Uncertain significance (Jul 06, 2020)	no assertion criteria provided Method: clinical testing	Carnitine deficiency Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV002078305.1 First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022
Uncertain significance (Jul 06, 2020)	no assertion criteria provided Method: clinical testing	Renal carnitine transport defect Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV002107429.1 First in ClinVar: Mar 28, 2022 Last updated: Mar 28, 2022

Comment:

This variant is present in population databases (rs759925126, gnomAD 0.0009%). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC22A5 protein function. ClinVar contains an entry for this variant (Variation ID: 947886). This missense change has been observed in individual(s) with clinical features of SLC22A5-related conditions (PMID: 35095998; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 157 of the SLC22A5 protein (p.Ser157Phe).

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Spectrum Analysis of Inherited Metabolic Disorders for Expanded Newborn Screening in a Central Chinese Population.	Li X	Frontiers in genetics	2022	PMID: 35095998

Text-mined citations for rs759925126 ...

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 Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_003060.4(SLC22A5):c.470C>T (p.Ser157Phe)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs759925126 ...