rs200370925
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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.658C>T(p.Arg220Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000372 in 1,614,046 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 (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
VIPAS39
NM_001193315.2 stop_gained
NM_001193315.2 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 5.47
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 14-77442636-G-A is Pathogenic according to our data. Variant chr14-77442636-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 113.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-77442636-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VIPAS39 | NM_001193315.2 | c.658C>T | p.Arg220Ter | stop_gained | 10/20 | ENST00000557658.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VIPAS39 | ENST00000557658.6 | c.658C>T | p.Arg220Ter | stop_gained | 10/20 | 1 | NM_001193315.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461852Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727224
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74330
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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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Name
Calibrated prediction
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Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A;A;A;A
Vest4
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 26
Find out detailed SpliceAI scores and Pangolin per-transcript scores at