NM_017866.6:c.580G>A
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_017866.6(TMEM70):c.580G>A(p.Val194Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,614,142 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V194L) has been classified as Uncertain significance.
Frequency
Consequence
NM_017866.6 missense
Scores
Clinical Significance
Conservation
Publications
- mitochondrial complex V (ATP synthase) deficiency, nuclear type 2Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
- mitochondrial diseaseInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
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ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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TMEM70 | NM_017866.6 | c.580G>A | p.Val194Met | missense_variant | Exon 3 of 3 | ENST00000312184.6 | NP_060336.3 | |
TMEM70 | NR_033334.2 | n.760G>A | non_coding_transcript_exon_variant | Exon 4 of 4 | ||||
TMEM70 | NM_001040613.3 | c.*270G>A | 3_prime_UTR_variant | Exon 3 of 3 | NP_001035703.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0106 AC: 1612AN: 152204Hom.: 9 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0125 AC: 3141AN: 251422 AF XY: 0.0126 show subpopulations
GnomAD4 exome AF: 0.0139 AC: 20381AN: 1461820Hom.: 180 Cov.: 33 AF XY: 0.0139 AC XY: 10078AN XY: 727202 show subpopulations
GnomAD4 genome AF: 0.0106 AC: 1613AN: 152322Hom.: 9 Cov.: 33 AF XY: 0.0101 AC XY: 753AN XY: 74492 show subpopulations
ClinVar
Submissions by phenotype
not provided Benign:3
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Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 Benign:2
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
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not specified Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at