10-100526447-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_005004.4(NDUFB8):c.420G>T(p.Met140Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,094 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 (★).
Frequency
Consequence
NM_005004.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NDUFB8 | NM_005004.4 | c.420G>T | p.Met140Ile | missense_variant | Exon 4 of 5 | ENST00000299166.9 | NP_004995.1 | |
NDUFB8 | NM_001284367.2 | c.420G>T | p.Met140Ile | missense_variant | Exon 4 of 5 | NP_001271296.1 | ||
NDUFB8 | NM_001284368.1 | c.327G>T | p.Met109Ile | missense_variant | Exon 4 of 5 | NP_001271297.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NDUFB8 | ENST00000299166.9 | c.420G>T | p.Met140Ile | missense_variant | Exon 4 of 5 | 1 | NM_005004.4 | ENSP00000299166.4 | ||
ENSG00000255339 | ENST00000557395.5 | n.420G>T | non_coding_transcript_exon_variant | Exon 4 of 10 | 2 | ENSP00000456832.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460094Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726412
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 140 of the NDUFB8 protein (p.Met140Ile). This variant is not present in population databases (gnomAD no frequency). 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: 1418766). 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 disruptive. 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