10-100529402-GT-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005004.4(NDUFB8):c.189delA(p.Glu63AspfsTer35) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,460 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_005004.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NDUFB8 | NM_005004.4 | c.189delA | p.Glu63AspfsTer35 | frameshift_variant | Exon 2 of 5 | ENST00000299166.9 | NP_004995.1 | |
NDUFB8 | NM_001284367.2 | c.189delA | p.Glu63AspfsTer35 | frameshift_variant | Exon 2 of 5 | NP_001271296.1 | ||
NDUFB8 | NM_001284368.1 | c.96delA | p.Glu32AspfsTer35 | frameshift_variant | Exon 2 of 5 | NP_001271297.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NDUFB8 | ENST00000299166.9 | c.189delA | p.Glu63AspfsTer35 | frameshift_variant | Exon 2 of 5 | 1 | NM_005004.4 | ENSP00000299166.4 | ||
ENSG00000255339 | ENST00000557395.5 | n.189delA | non_coding_transcript_exon_variant | Exon 2 of 10 | 2 | ENSP00000456832.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249838Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135124
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460336Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 726480
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74298
ClinVar
Submissions by phenotype
Mitochondrial complex 1 deficiency, nuclear type 32 Pathogenic:1
- -
not provided Uncertain:1
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. ClinVar contains an entry for this variant (Variation ID: 548133). This premature translational stop signal has been observed in individual(s) with mitochondrial complex I deficiency (PMID: 29429571). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Glu63Aspfs*35) in the NDUFB8 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NDUFB8 cause disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at