VCV000140592.4 - ClinVar

NC_012920.1(MT-CYB):m.15326A>G

Germline

Top reviewed classifications are shown here.

Submission summary:

3 submissions

3 submitters

3 conditions

Reviewed by expert panel

Benign

Mar 2022 by ClinGen Mitoch… FDA Recognized Database

for Mitochondrial disease

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_012920.1(MT-CYB):m.15326A>G

Variation ID: 140592 Accession: VCV000140592.4

Type and length

single nucleotide variant, 1 bp

Location

MT: 15326 (GRCh38) [ NCBI UCSC ] MT: 15326 (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 25, 2014	Apr 16, 2022	Mar 24, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NC_012920.1:m.15326A>G

Protein change

Other names

Canonical SPDI

NC_012920.1:15325:A:G

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

ClinGen: CA269989 dbSNP: rs2853508 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.
MT-CYB		-	-	GRCh38	321	328

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.
Familial cancer of breast	Likely pathogenic (1)	no assertion criteria provided	-	RCV000128807.3
Leigh syndrome	Benign (1)	criteria provided, single submitter	Oct 17, 2019	RCV000855273.2
Mitochondrial disease	Benign (1)	reviewed by expert panel	Mar 24, 2022	RCV002221492.2

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.
Benign (Mar 24, 2022)	reviewed by expert panel (clingen mito disease acmg specifications v1-1) Method: curation	Mitochondrial disease (Mitochondrial inheritance) Affected status: unknown Allele origin: germline	ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen FDA Recognized Database Accession: SCV002498776.1 First in ClinVar: Apr 16, 2022 Last updated: Apr 16, 2022	Other databases https://erepo.clinicalgenome.org… https://erepo.clinicalgenome.org/evrepo/ui/interpretation/6b61c78a-7eec-4bcc-93a2-b497b62f93c7 Comment: The m.15326A>G (p.T194A) variant in MT-CYB was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot … (more) The m.15326A>G (p.T194A) variant in MT-CYB was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot for mitochondrial DNA variant specifications (McCormick et al., 2020; PMID: 32906214). This variant is seen at high frequencies in numerous haplogroups and the overall allele frequency in GenBank database (per Mitomap; queried 6/29/2020) is 98.7% (BA1). Additionally, the computational predictor APOGEE gives a consensus rating of neutral with a low pathogenicity predictor score, 0.4 (Min=0, Max=1), evidence that does not predict a damaging effect on gene function (BP4). In summary, this variant meets criteria to be classified as benign. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel as of August 20, 2020. Mitochondrial DNA-specific ACMG/AMP criteria applied: BA1, BP4. (less)
Benign (Oct 17, 2019)	criteria provided, single submitter (Modified ACMG Guidelines (Unpublished)) Method: clinical testing	Leigh syndrome Affected status: unknown Allele origin: germline	Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine Accession: SCV000998323.1 First in ClinVar: Nov 02, 2019 Last updated: Nov 02, 2019	Comment: The NC_012920.1:m.15326A>G (YP_003024038.1:p.Thr194Ala) variant in MTCYB gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the … (more) The NC_012920.1:m.15326A>G (YP_003024038.1:p.Thr194Ala) variant in MTCYB gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BA1 (less)
probable-pathogenic (-)	no assertion criteria provided Method: not provided	Familial cancer of breast Affected status: not provided Allele origin: unknown	Department of Zoology Govt. MVM College Accession: SCV000172465.1 First in ClinVar: Jul 25, 2014 Last updated: Jul 25, 2014 Comment: Our Seq: KM077020	Comment: Converted during submission to Likely pathogenic.

Comment:

The m.15326A>G (p.T194A) variant in MT-CYB was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot for mitochondrial DNA variant specifications (McCormick et al., 2020; PMID: 32906214). This variant is seen at high frequencies in numerous haplogroups and the overall allele frequency in GenBank database (per Mitomap; queried 6/29/2020) is 98.7% (BA1). Additionally, the computational predictor APOGEE gives a consensus rating of neutral with a low pathogenicity predictor score, 0.4 (Min=0, Max=1), evidence that does not predict a damaging effect on gene function (BP4). In summary, this variant meets criteria to be classified as benign. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel as of August 20, 2020. Mitochondrial DNA-specific ACMG/AMP criteria applied: BA1, BP4.

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
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/6b61c78a-7eec-4bcc-93a2-b497b62f93c7	-	-	-	-

Text-mined citations for rs2853508 ...

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 Sep 08, 2024

ClinVar Genomic variation as it relates to human health

NC_012920.1(MT-CYB):m.15326A>G

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs2853508 ...