15-41396968-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_016013.4(NDUFAF1):c.92G>A(p.Arg31His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,611,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R31C) has been classified as Uncertain significance.
Frequency
Consequence
NM_016013.4 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NDUFAF1 | NM_016013.4 | c.92G>A | p.Arg31His | missense_variant | Exon 2 of 5 | ENST00000260361.9 | NP_057097.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151874Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249374Hom.: 0 AF XY: 0.0000592 AC XY: 8AN XY: 135090
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1459806Hom.: 0 Cov.: 34 AF XY: 0.0000482 AC XY: 35AN XY: 726112
GnomAD4 genome AF: 0.0000263 AC: 4AN: 151992Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74256
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 31 of the NDUFAF1 protein (p.Arg31His). This variant is present in population databases (rs3204853, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with NDUFAF1-related conditions. Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt NDUFAF1 protein function with a negative predictive value of 80%. 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