22-42086235-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_002490.6(NDUFA6):c.335C>T(p.Ala112Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002490.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NDUFA6 | NM_002490.6 | c.335C>T | p.Ala112Val | missense_variant | 3/3 | ENST00000498737.8 | NP_002481.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NDUFA6 | ENST00000498737.8 | c.335C>T | p.Ala112Val | missense_variant | 3/3 | 1 | NM_002490.6 | ENSP00000418842 | P1 | |
NDUFA6 | ENST00000617763.1 | c.413C>T | p.Ala138Val | missense_variant | 3/3 | 1 | ENSP00000482543 | |||
NDUFA6 | ENST00000470753.1 | c.164C>T | p.Ala55Val | missense_variant | 2/2 | 2 | ENSP00000473478 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251486Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135916
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727242
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 04, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 138 of the NDUFA6 protein (p.Ala138Val). This variant is present in population databases (rs776731051, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with NDUFA6-related conditions. 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at