8-124539250-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005005.3(NDUFB9):c.64C>T(p.Arg22Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R22Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_005005.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251016Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135822
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461874Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6AN XY: 727236
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.64C>T (p.R22W) alteration is located in exon 1 (coding exon 1) of the NDUFB9 gene. This alteration results from a C to T substitution at nucleotide position 64, causing the arginine (R) at amino acid position 22 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 22 of the NDUFB9 protein (p.Arg22Trp). This variant is present in population databases (rs759625380, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with NDUFB9-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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