VCV001929400.5 - ClinVar

NM_014251.3(SLC25A13):c.1769C>A (p.Ser590Ter)

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.

(2)

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/Likely 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_014251.3(SLC25A13):c.1769C>A (p.Ser590Ter)

Variation ID: 1929400 Accession: VCV001929400.5

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q21.3 7: 96121727 (GRCh38) [ NCBI UCSC ] 7: 95751039 (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 7, 2023	Jun 17, 2024	Jan 2, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_014251.3:c.1769C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_055066.1:p.Ser590Ter	nonsense
NM_001160210.2:c.1772C>A	NP_001153682.1:p.Ser591Ter	nonsense
NR_027662.2:n.1795C>A		non-coding transcript variant
NC_000007.14:g.96121727G>T
NC_000007.13:g.95751039G>T
NG_012247.2:g.205421C>A

... more HGVS ... less HGVS

Protein change

S590*, S591*

Other names

Canonical SPDI

NC_000007.14:96121726:G: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.

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.
SLC25A13		-	-	GRCh38 GRCh37	844	890

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.
Citrin deficiency	Pathogenic (1)	criteria provided, single submitter	Aug 22, 2022	RCV002635333.3
Citrullinemia, type II, adult-onset	Likely pathogenic (1)	criteria provided, single submitter	Jan 2, 2024	RCV003475406.2

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 (Aug 22, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Citrin deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002961402.2 First in ClinVar: Feb 07, 2023 Last updated: Feb 28, 2024	Publications: PubMed (4) PubMed: 31980526‚ 10369257‚ 14680984‚ 27405544 Comment: For these reasons, this variant has been classified as Pathogenic. This variant is also known as c.1772C>A (p.Ser591). This premature translational stop signal has been … (more) For these reasons, this variant has been classified as Pathogenic. This variant is also known as c.1772C>A (p.Ser591). This premature translational stop signal has been observed in individual(s) with citrullinemia (PMID: 31980526). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser590*) in the SLC25A13 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC25A13 are known to be pathogenic (PMID: 10369257, 14680984, 27405544). (less)
Likely pathogenic (Jan 02, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Citrullinemia, type II, adult-onset Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004201657.2 First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024

Comment:

For these reasons, this variant has been classified as Pathogenic. This variant is also known as c.1772C>A (p.Ser591*). This premature translational stop signal has been observed in individual(s) with citrullinemia (PMID: 31980526). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser590*) in the SLC25A13 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC25A13 are known to be pathogenic (PMID: 10369257, 14680984, 27405544).

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
Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging.	Hou YC	Proceedings of the National Academy of Sciences of the United States of America	2020	PMID: 31980526
Molecular diagnosis of pediatric patients with citrin deficiency in China: SLC25A13 mutation spectrum and the geographic distribution.	Lin WX	Scientific reports	2016	PMID: 27405544
Screening of nine SLC25A13 mutations: their frequency in patients with citrin deficiency and high carrier rates in Asian populations.	Kobayashi K	Molecular genetics and metabolism	2003	PMID: 14680984
The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein.	Kobayashi K	Nature genetics	1999	PMID: 10369257

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_014251.3(SLC25A13):c.1769C>A (p.Ser590Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...