VCV000842614.14 - ClinVar

NM_003060.4(SLC22A5):c.825-52G>A

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.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_003060.4(SLC22A5):c.825-52G>A

Variation ID: 842614 Accession: VCV000842614.14

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q31.1 5: 132386973 (GRCh38) [ NCBI UCSC ] 5: 131722665 (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 15, 2020	Jun 17, 2024	Mar 3, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_003060.4:c.825-52G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001308122.2:c.897-52G>A		intron variant
NC_000005.10:g.132386973G>A
NC_000005.9:g.131722665G>A
NG_008982.2:g.22270G>A

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000005.10:132386972:G:A

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.

Trans-Omics for Precision Medicine (TOPMed) 0.00001

Links

dbSNP: rs1194929977 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.
Renal carnitine transport defect	Pathogenic (3)	criteria provided, multiple submitters, no conflicts	Mar 3, 2024	RCV001045059.19
Decreased circulating carnitine concentration	Pathogenic (1)	no assertion criteria provided	Jul 8, 2021	RCV002226510.9

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 (Oct 08, 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: SCV001208889.5 First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024	Publications: PubMed (1) PubMed: 23963628 Comment: This sequence change falls in intron 4 of the SLC22A5 gene. It does not directly change the encoded amino acid sequence of the SLC22A5 protein. … (more) This sequence change falls in intron 4 of the SLC22A5 gene. It does not directly change the encoded amino acid sequence of the SLC22A5 protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with primary carnitine deficiency (PMID: 23963628). ClinVar contains an entry for this variant (Variation ID: 842614). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Mar 03, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Renal carnitine transport defect Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004203568.2 First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024
Pathogenic (Jul 08, 2021)	no assertion criteria provided Method: clinical testing	Carnitine deficiency Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV002078321.1 First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022
Pathogenic (Jul 08, 2021)	no assertion criteria provided Method: clinical testing	Renal carnitine transport defect Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV002107444.1 First in ClinVar: Mar 28, 2022 Last updated: Mar 28, 2022

Comment:

This sequence change falls in intron 4 of the SLC22A5 gene. It does not directly change the encoded amino acid sequence of the SLC22A5 protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with primary carnitine deficiency (PMID: 23963628). ClinVar contains an entry for this variant (Variation ID: 842614). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.

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
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

Text-mined citations for rs1194929977 ...

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.825-52G>A

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1194929977 ...