rs104893631
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_080916.3(DGUOK):c.425G>A(p.Arg142Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,556 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 Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R142R) has been classified as Likely benign.
Frequency
Consequence
NM_080916.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DGUOK | NM_080916.3 | c.425G>A | p.Arg142Lys | missense_variant | 3/7 | ENST00000264093.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGUOK | ENST00000264093.9 | c.425G>A | p.Arg142Lys | missense_variant | 3/7 | 1 | NM_080916.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249510Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134820
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1460404Hom.: 0 Cov.: 32 AF XY: 0.00000964 AC XY: 7AN XY: 726438
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74324
ClinVar
Submissions by phenotype
Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2002 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 16, 2019 | Published functional studies demonstrate R142K results in decreased enzyme activity, supporting a damaging effect (Wang et al., 2003); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 12205643, 18600543, 14623087) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at