rs886037846
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_080916.3(DGUOK):āc.797T>Gā(p.Leu266Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,624 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L266F) has been classified as Uncertain significance.
Frequency
Consequence
NM_080916.3 missense
Scores
Clinical Significance
Conservation
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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.797T>G | p.Leu266Arg | missense_variant | 6/7 | ENST00000264093.9 | |
DGUOK-AS1 | NR_104030.1 | n.306-28A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGUOK | ENST00000264093.9 | c.797T>G | p.Leu266Arg | missense_variant | 6/7 | 1 | NM_080916.3 | P1 | |
DGUOK-AS1 | ENST00000667561.3 | n.308-10300A>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460624Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726686
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2007 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 27, 2023 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DGUOK protein function. ClinVar contains an entry for this variant (Variation ID: 253063). This missense change has been observed in individual(s) with mtDNA depletion syndrome (PMID: 16263314, 17073823). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 266 of the DGUOK protein (p.Leu266Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at