rs869312811
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_020821.3(VPS13C):c.4777delC(p.Gln1593fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
VPS13C
NM_020821.3 frameshift
NM_020821.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.514
Genes affected
VPS13C (HGNC:23594): (vacuolar protein sorting 13 homolog C) Involved in mitochondrion organization and negative regulation of parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization. Located in cytosol and mitochondrial outer membrane. Implicated in Parkinson's disease 23. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-61947291-TG-T is Pathogenic according to our data. Variant chr15-61947291-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 222071.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-61947291-TG-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS13C | NM_020821.3 | c.4777delC | p.Gln1593fs | frameshift_variant | 43/85 | ENST00000644861.2 | NP_065872.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VPS13C | ENST00000644861.2 | c.4777delC | p.Gln1593fs | frameshift_variant | 43/85 | NM_020821.3 | ENSP00000493560.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1456316Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 724478
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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1456316
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30
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0
AN XY:
724478
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive early-onset Parkinson disease 23 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 20, 2019 | - - |
Parkinson disease Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Brain and Spine Institute, INSERM | Nov 16, 2015 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at