NM_017866.6(TMEM70):c.293G>A (p.Gly98Asp) AND Mitochondrial complex V (ATP synthase) deficiency nuclear type 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 13, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003006345.2

Allele description [Variation Report for NM_017866.6(TMEM70):c.293G>A (p.Gly98Asp)]

NM_017866.6(TMEM70):c.293G>A (p.Gly98Asp)

Gene:

TMEM70:transmembrane protein 70 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q21.11

Genomic location:

Preferred name:

NM_017866.6(TMEM70):c.293G>A (p.Gly98Asp)

HGVS:

NC_000008.11:g.73978838G>A
NG_016618.1:g.7697G>A
NM_001040613.3:c.293G>A
NM_017866.6:c.293G>AMANE SELECT
NP_001035703.1:p.Gly98Asp
NP_060336.3:p.Gly98Asp
NC_000008.10:g.74891073G>A
NR_033334.2:n.380G>A

Protein change:

G98D

Molecular consequence:

NM_001040613.3:c.293G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_017866.6:c.293G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_033334.2:n.380G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Mitochondrial complex V (ATP synthase) deficiency nuclear type 2
Synonyms:: ENCEPHALOCARDIOMYOPATHY, MITOCHONDRIAL, NEONATAL, DUE TO ATP SYNTHASE DEFICIENCY; MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, TMEM70 TYPE; Nuclearly-encoded mitochondrial complex V (ATP synthase) deficiency 2; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013546; MedGen: C3279699; Orphanet: 1194; OMIM: 614052

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003311992	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 13, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003311992

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 13, 2022)

germline

clinical testing

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

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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	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003311992.2

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with TMEM70-related conditions. This variant is present in population databases (rs141592371, gnomAD 0.008%). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 98 of the TMEM70 protein (p.Gly98Asp).

#	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: Feb 20, 2024

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