NM_004046.6(ATP5F1A):c.962A>G (p.Tyr321Cys) AND Combined oxidative phosphorylation deficiency 22

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 7, 2013
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000144489.8

Allele description [Variation Report for NM_004046.6(ATP5F1A):c.962A>G (p.Tyr321Cys)]

NM_004046.6(ATP5F1A):c.962A>G (p.Tyr321Cys)

Gene:

ATP5F1A:ATP synthase F1 subunit alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q21.1

Genomic location:

Preferred name:

NM_004046.6(ATP5F1A):c.962A>G (p.Tyr321Cys)

HGVS:

NC_000018.10:g.46087222T>C
NG_041769.2:g.27012A>G
NM_001001935.3:c.812A>G
NM_001001937.2:c.962A>G
NM_001257334.2:c.896A>G
NM_001257335.2:c.812A>G
NM_004046.6:c.962A>GMANE SELECT
NP_001001935.1:p.Tyr271Cys
NP_001001937.1:p.Tyr321Cys
NP_001244263.1:p.Tyr299Cys
NP_001244264.1:p.Tyr271Cys
NP_004037.1:p.Tyr321Cys
NC_000018.9:g.43667188T>C
NM_004046.5:c.962A>G
P25705:p.Tyr321Cys

Protein change:

Y271C; TYR321CYS

Links:

UniProtKB: P25705#VAR_071982; OMIM: 164360.0002; dbSNP: rs587777788

NCBI 1000 Genomes Browser:

rs587777788

Molecular consequence:

NM_001001935.3:c.812A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001001937.2:c.962A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001257334.2:c.896A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001257335.2:c.812A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004046.6:c.962A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Combined oxidative phosphorylation deficiency 22 (COXPD22)
Identifiers:: MONDO: MONDO:0020727; MedGen: C4015062; OMIM: 616045

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000189820	OMIM	no assertion criteria provided	Pathogenic (May 7, 2013)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000189820

OMIM

no assertion criteria provided

Pathogenic
(May 7, 2013)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Targeted exome sequencing of suspected mitochondrial disorders.

Lieber DS, Calvo SE, Shanahan K, Slate NG, Liu S, Hershman SG, Gold NB, Chapman BA, Thorburn DR, Berry GT, Schmahmann JD, Borowsky ML, Mueller DM, Sims KB, Mootha VK.

Neurology. 2013 May 7;80(19):1762-70. doi: 10.1212/WNL.0b013e3182918c40. Epub 2013 Apr 17.

PubMed [citation]

PMID:: 23596069
PMCID:: PMC3719425

Details of each submission

From OMIM, SCV000189820.7

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

Description

In 2 sisters, born of consanguineous Moroccan parents, with combined oxidative phosphorylation deficiency (COXPD22; 616045) resulting in early death, Lieber et al. (2013) identified a homozygous c.962A-G transition in the ATP5A1 gene, resulting in a tyr321-to-cys (Y321C) substitution at a highly conserved residue. The variant, which was found by targeted exome sequencing of the mitochondrial genome and nuclear-encoded genes implicated in mitochondrial biology, was not present in the 1000 Genomes Project or Exome Variant Server databases. The unaffected mother was heterozygous for the mutation; DNA from the father was unavailable. Expression of the analogous mutation in yeast resulted in an increased rate of mtDNA loss and a 2-fold decrease in mitochondrial membrane potential compared to wildtype.

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

Last Updated: May 13, 2023

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