rs761158492
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_031310.3(PLVAP):c.1072C>T(p.Arg358Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,002 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: not found (cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
PLVAP
NM_031310.3 stop_gained
NM_031310.3 stop_gained
Scores
2
1
4
Clinical Significance
Conservation
PhyloP100: -0.0750
Genes affected
PLVAP (HGNC:13635): (plasmalemma vesicle associated protein) Predicted to enable identical protein binding activity. Involved in MAPK cascade; positive regulation of cellular extravasation; and tumor necrosis factor-mediated signaling pathway. Located in cell surface. Colocalizes with caveola. Implicated in congenital diarrhea. [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 19-17365393-G-A is Pathogenic according to our data. Variant chr19-17365393-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 590326.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLVAP | NM_031310.3 | c.1072C>T | p.Arg358Ter | stop_gained | 3/6 | ENST00000252590.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLVAP | ENST00000252590.9 | c.1072C>T | p.Arg358Ter | stop_gained | 3/6 | 1 | NM_031310.3 | P1 | |
PLVAP | ENST00000595816.1 | c.79+580C>T | intron_variant | 3 | |||||
PLVAP | ENST00000599426.1 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250766Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135648
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461002Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 726882
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GnomAD4 genome ? Cov.: 32
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?
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32
ExAC
?
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Diarrhea 10, protein-losing enteropathy type Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 20, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
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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