rs387906345
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_139027.6(ADAMTS13):c.291_319delGGAGGACACAGAGCGCTATGTGCTCACCA(p.Glu98fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,622 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: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
ADAMTS13
NM_139027.6 frameshift
NM_139027.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.65
Genes affected
ADAMTS13 (HGNC:1366): (ADAM metallopeptidase with thrombospondin type 1 motif 13) This gene encodes a member of a family of proteins containing several distinct regions, including a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. The enzyme encoded by this gene specifically cleaves von Willebrand Factor (vWF). Defects in this gene are associated with thrombotic thrombocytopenic purpura. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
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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 9-133424430-GGCTCACCAGGAGGACACAGAGCGCTATGT-G is Pathogenic according to our data. Variant chr9-133424430-GGCTCACCAGGAGGACACAGAGCGCTATGT-G is described in ClinVar as [Pathogenic]. Clinvar id is 5820.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAMTS13 | NM_139027.6 | c.291_319delGGAGGACACAGAGCGCTATGTGCTCACCA | p.Glu98fs | frameshift_variant | 3/29 | ENST00000355699.7 | NP_620596.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADAMTS13 | ENST00000355699.7 | c.291_319delGGAGGACACAGAGCGCTATGTGCTCACCA | p.Glu98fs | frameshift_variant | 3/29 | 1 | NM_139027.6 | ENSP00000347927.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461622Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727098
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727098
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
Bravo
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Upshaw-Schulman syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2004 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at