rs794726653
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001193315.2(VIPAS39):c.749_753del(p.Thr250ArgfsTer17) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,296 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
VIPAS39
NM_001193315.2 frameshift
NM_001193315.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.45
Genes affected
VIPAS39 (HGNC:20347): (VPS33B interacting protein, apical-basolateral polarity regulator, spe-39 homolog) Involved in endosome to lysosome transport and intracellular protein transport. Acts upstream of or within collagen metabolic process and peptidyl-lysine hydroxylation. Located in Golgi apparatus and endosome. Implicated in arthrogryposis, renal dysfunction, and cholestasis 2. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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 14-77441074-CTTCTG-C is Pathogenic according to our data. Variant chr14-77441074-CTTCTG-C is described in ClinVar as [Pathogenic]. Clinvar id is 112.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-77441074-CTTCTG-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VIPAS39 | NM_001193315.2 | c.749_753del | p.Thr250ArgfsTer17 | frameshift_variant | 11/20 | ENST00000557658.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VIPAS39 | ENST00000557658.6 | c.749_753del | p.Thr250ArgfsTer17 | frameshift_variant | 11/20 | 1 | NM_001193315.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
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33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251454Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135902
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461296Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726974
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Arthrogryposis, renal dysfunction, and cholestasis 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2010 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at