rs1057519063
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_018668.5(VPS33B):c.319C>T(p.Arg107Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,858 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_018668.5 stop_gained
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 |
---|---|---|---|---|---|---|---|
VPS33B | NM_018668.5 | c.319C>T | p.Arg107Ter | stop_gained | 5/23 | ENST00000333371.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS33B | ENST00000333371.8 | c.319C>T | p.Arg107Ter | stop_gained | 5/23 | 1 | NM_018668.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461858Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727238
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 375326). This variant is also known as p.Arg97X. This premature translational stop signal has been observed in individual(s) with arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome (PMID: 16896922). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg107*) in the VPS33B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in VPS33B are known to be pathogenic (PMID: 15052268, 16896922). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at