rs886037615
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_080916.3(DGUOK):c.609_610del(p.Tyr204ProfsTer11) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000342 in 1,461,636 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L203L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_080916.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DGUOK | NM_080916.3 | c.609_610del | p.Tyr204ProfsTer11 | frameshift_variant | 5/7 | ENST00000264093.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGUOK | ENST00000264093.9 | c.609_610del | p.Tyr204ProfsTer11 | frameshift_variant | 5/7 | 1 | NM_080916.3 | P1 | |
DGUOK-AS1 | ENST00000667561.3 | n.308-9207_308-9206del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461636Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727140
GnomAD4 genome ? Cov.: 32
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 | Invitae | Jul 25, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 8156). This premature translational stop signal has been observed in individual(s) with mitochondrial DNA depletion (PMID: 12205643). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr204Profs*11) in the DGUOK gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DGUOK are known to be pathogenic (PMID: 18205204). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at