rs121908476
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The ENST00000355699.7(ADAMTS13):āc.1345C>Gā(p.Gln449Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,435,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Exomes š: 7.0e-7 ( 0 hom. )
Consequence
ADAMTS13
ENST00000355699.7 missense
ENST00000355699.7 missense
Scores
7
9
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.29
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.913
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAMTS13 | NM_139027.6 | c.1345C>G | p.Gln449Glu | missense_variant | 12/29 | ENST00000355699.7 | NP_620596.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADAMTS13 | ENST00000355699.7 | c.1345C>G | p.Gln449Glu | missense_variant | 12/29 | 1 | NM_139027.6 | ENSP00000347927 | A2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000486 AC: 1AN: 205952Hom.: 0 AF XY: 0.00000898 AC XY: 1AN XY: 111298
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GnomAD4 exome AF: 6.96e-7 AC: 1AN: 1435866Hom.: 0 Cov.: 35 AF XY: 0.00000140 AC XY: 1AN XY: 711752
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GnomAD4 genome Cov.: 31
GnomAD4 genome
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31
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D;D;T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;H;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D
REVEL
Uncertain
Sift
Pathogenic
D;.;D;D
Sift4G
Uncertain
D;D;D;.
Polyphen
D;.;D;D
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.1571);.;Gain of relative solvent accessibility (P = 0.1571);.;
MVP
MPC
ClinPred
D
GERP RS
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gMVP
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