chr10-100529820-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_005004.4(NDUFB8):c.32T>C(p.Val11Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,612,570 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V11V) has been classified as Likely benign.
Frequency
Consequence
NM_005004.4 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDUFB8 | NM_005004.4 | c.32T>C | p.Val11Ala | missense_variant | 1/5 | ENST00000299166.9 | |
NDUFB8 | NM_001284367.2 | c.32T>C | p.Val11Ala | missense_variant | 1/5 | ||
NDUFB8 | NM_001284368.1 | c.-9+38T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDUFB8 | ENST00000299166.9 | c.32T>C | p.Val11Ala | missense_variant | 1/5 | 1 | NM_005004.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000238 AC: 36AN: 151298Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000918 AC: 23AN: 250426Hom.: 1 AF XY: 0.0000812 AC XY: 11AN XY: 135450
GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461158Hom.: 1 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 726878
GnomAD4 genome ? AF: 0.000238 AC: 36AN: 151412Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12AN XY: 73966
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 05, 2024 | The c.32T>C (p.V11A) alteration is located in exon 1 (coding exon 1) of the NDUFB8 gene. This alteration results from a T to C substitution at nucleotide position 32, causing the valine (V) at amino acid position 11 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 22, 2023 | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 11 of the NDUFB8 protein (p.Val11Ala). This variant is present in population databases (rs146449373, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with NDUFB8-related conditions. ClinVar contains an entry for this variant (Variation ID: 1407999). 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