VCV002850562.1 - ClinVar

NM_012434.5(SLC17A5):c.3del (p.Met1fs)

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.

(1)

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, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_012434.5(SLC17A5):c.3del (p.Met1fs)

Variation ID: 2850562 Accession: VCV002850562.1

Type and length

Deletion, 1 bp

Location

Cytogenetic: 6q13 6: 73653884 (GRCh38) [ NCBI UCSC ] 6: 74363607 (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	Feb 20, 2024	Feb 20, 2024	Mar 29, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_012434.5:c.3del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_036566.1:p.Met1fs	frameshift initiator codon variant
NM_001382629.1:c.-32del		5 prime UTR
NM_001382630.1:c.3del	NP_001369559.1:p.Met1fs	frameshift initiator codon variant
NM_001382631.1:c.3del	NP_001369560.1:p.Met1fs	frameshift initiator codon variant
NM_001382632.1:c.3del	NP_001369561.1:p.Met1fs	frameshift initiator codon variant
NM_001382633.1:c.3del	NP_001369562.1:p.Met1fs	frameshift initiator codon variant
NM_001382634.1:c.3del	NP_001369563.1:p.Met1fs	frameshift initiator codon variant
NM_001382635.1:c.3del	NP_001369564.1:p.Met1fs	frameshift initiator codon variant
NM_001382636.1:c.-32del		5 prime UTR
NC_000006.12:g.73653884del
NC_000006.11:g.74363607del
NG_008272.1:g.5131del
NG_176173.1:g.547del

... more HGVS ... less HGVS

Protein change

M1fs

Other names

Canonical SPDI

NC_000006.12:73653883:C:

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.

Links

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.
LOC129996727	-	-	-	GRCh38	-	55
SLC17A5		-	-	GRCh38 GRCh37	566	663

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.
Salla disease	Pathogenic (1)	criteria provided, single submitter	Mar 29, 2023	RCV003614710.2

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 (Mar 29, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Salla disease Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004448849.1 First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024	Publications: PubMed (8) PubMed: 10581036‚ 10947946‚ 12359136‚ 12794688‚ 15510212‚ 15516337‚ 18695252‚ 21781115 Comment: For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SLC17A5 protein in which other variant(s) (p.Arg39Cys ) … (more) For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SLC17A5 protein in which other variant(s) (p.Arg39Cys ) have been determined to be pathogenic (PMID: 10581036, 10947946, 12359136, 12794688, 15510212, 15516337, 18695252, 21781115). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with SLC17A5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the SLC17A5 mRNA. The next in-frame methionine is located at codon 67. (less)

Comment:

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SLC17A5 protein in which other variant(s) (p.Arg39Cys ) have been determined to be pathogenic (PMID: 10581036, 10947946, 12359136, 12794688, 15510212, 15516337, 18695252, 21781115). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with SLC17A5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the SLC17A5 mRNA. The next in-frame methionine is located at codon 67.

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
Functional characterization of vesicular excitatory amino acid transport by human sialin.	Miyaji T	Journal of neurochemistry	2011	PMID: 21781115
Identification of a vesicular aspartate transporter.	Miyaji T	Proceedings of the National Academy of Sciences of the United States of America	2008	PMID: 18695252
Varied mechanisms underlie the free sialic acid storage disorders.	Wreden CC	The Journal of biological chemistry	2005	PMID: 15516337
Functional characterization of wild-type and mutant human sialin.	Morin P	The EMBO journal	2004	PMID: 15510212
Biochemical and molecular analyses of infantile free sialic acid storage disease in North American children.	Kleta R	American journal of medical genetics. Part A	2003	PMID: 12794688
Unraveling the molecular pathogenesis of free sialic acid storage disorders: altered targeting of mutant sialin.	Aula N	Molecular genetics and metabolism	2002	PMID: 12359136
The spectrum of SLC17A5-gene mutations resulting in free sialic acid-storage diseases indicates some genotype-phenotype correlation.	Aula N	American journal of human genetics	2000	PMID: 10947946
A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases.	Verheijen FW	Nature genetics	1999	PMID: 10581036

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NM_012434.5(SLC17A5):c.3del (p.Met1fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...