rs28939679
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM1PM2PP3_ModeratePP5_Very_Strong
The NM_002496.4(NDUFS8):c.236C>T(p.Pro79Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,558 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 Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. P79P) has been classified as Likely benign.
Frequency
Consequence
NM_002496.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDUFS8 | NM_002496.4 | c.236C>T | p.Pro79Leu | missense_variant | 5/7 | ENST00000313468.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDUFS8 | ENST00000313468.10 | c.236C>T | p.Pro79Leu | missense_variant | 5/7 | 1 | NM_002496.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000807 AC: 2AN: 247786Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134704
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460558Hom.: 0 Cov.: 34 AF XY: 0.00000826 AC XY: 6AN XY: 726622
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Leigh syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 10, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 20819849, 36557887, 9837812) - |
Mitochondrial complex 1 deficiency, nuclear type 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 1998 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at