rs143337739
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The ENST00000313468.10(NDUFS8):c.460G>A(p.Gly154Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,680 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
ENST00000313468.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NDUFS8 | NM_002496.4 | c.460G>A | p.Gly154Ser | missense_variant | 6/7 | ENST00000313468.10 | NP_002487.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NDUFS8 | ENST00000313468.10 | c.460G>A | p.Gly154Ser | missense_variant | 6/7 | 1 | NM_002496.4 | ENSP00000315774 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461456Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727032
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2024 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22142868, 33233646, 36557887, 36074903, 36101822, 20818383, 23430795) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 24, 2017 | - - |
Mitochondrial complex 1 deficiency, nuclear type 2 Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City | Feb 05, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at