NC_012920.1(MT-ATP6):m.8932C>T AND Mitochondrial disease

Germline classification:: Benign (1 submission)
Last evaluated:: Mar 22, 2021
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001526415.1

Allele description [Variation Report for NC_012920.1(MT-ATP6):m.8932C>T]

NC_012920.1(MT-ATP6):m.8932C>T

Gene:

MT-ATP6:mitochondrially encoded ATP synthase 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Genomic location:

Preferred name:

NC_012920.1(MT-ATP6):m.8932C>T

HGVS:

NC_012920.1:m.8932C>T

Links:

dbSNP: rs878853013

NCBI 1000 Genomes Browser:

rs878853013

Condition(s)

Name:: Mitochondrial disease
Synonyms:: Mitochondrial diseases; Mitochondrial disorder
Identifiers:: MONDO: MONDO:0044970; MeSH: D028361; MedGen: C0751651; Orphanet: 68380

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001736755	ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen	reviewed by expert panel (McCormick et al. (Hum Mutat. 2020))	Benign (Mar 22, 2021)	germline	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001736755

ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen

reviewed by expert panel

(McCormick et al. (Hum Mutat. 2020))

Benign
(Mar 22, 2021)

germline

curation

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Specifications of the ACMG/AMP standards and guidelines for mitochondrial DNA variant interpretation.

McCormick EM, Lott MT, Dulik MC, Shen L, Attimonelli M, Vitale O, Karaa A, Bai R, Pineda-Alvarez DE, Singh LN, Stanley CM, Wong S, Bhardwaj A, Merkurjev D, Mao R, Sondheimer N, Zhang S, Procaccio V, Wallace DC, Gai X, Falk MJ.

Hum Mutat. 2020 Dec;41(12):2028-2057. doi: 10.1002/humu.24107. Epub 2020 Nov 10.

PubMed [citation]

PMID:: 32906214
PMCID:: PMC7717623

Details of each submission

From ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen, SCV001736755.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

Description

The m.8932C>T (p.P136S) variant in MT-ATP6 reaches benign stand-alone criteria (BA1) based on overall allele frequency [gnomAD.v3.1: Overall AF is 1.327% (759/56428); in top-level haplogroup L3, AF is 12.89% (731/5669) Mitomap: Overall AF in Mitomap is 0.399% (207/51863; in top-level haplogroup L3, AF is 9.73%. For the individuals in sub-group L3f, the frequency is 81% (205/253)]. Furthermore, this variant is reported in Phylotree as an L3f1b branch marker. There is one reported proband in the medical literature with this variant (PMID: 26993169), however when haplotyped by this curation team using the variants listed in the published report, the proband belonged to haplogroup L3f (haplogroup with which this variant is associated). In silico tools (APOGEE) predict this variant to be neutral (BP4). There are no cybrid or single fiber studies reported on this variant. In summary, this variant meets criteria to be classified as benign for primary mitochondrial disease inherited in a mitochondrial manner. However, if this variant is identified in an individual who is a member of a different haplogroup than described above, consider further evaluation of this variant. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel on March 22, 2021. Mitochondrial DNA-specific ACMG/AMP criteria applied: BA1, BP4.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 19, 2024

ClinVar

Relating variation to medicine