9-133426266-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong

The NM_139027.6(ADAMTS13):​c.607T>C​(p.Ser203Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

ADAMTS13
NM_139027.6 missense

Scores

7
10
2

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 3.77
Variant links:
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 Likely_pathogenic. Variant got 8 ACMG points.

PM1
In a domain Peptidase M12B (size 206) in uniprot entity ATS13_HUMAN there are 14 pathogenic changes around while only 0 benign (100%) in NM_139027.6
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.984

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADAMTS13NM_139027.6 linkc.607T>C p.Ser203Pro missense_variant 6/29 ENST00000355699.7 NP_620596.2 Q76LX8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADAMTS13ENST00000355699.7 linkc.607T>C p.Ser203Pro missense_variant 6/291 NM_139027.6 ENSP00000347927.2 Q76LX8-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
33

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

not provided Other:1
not provided, no classification providedliterature onlyUniProtKB/Swiss-Prot-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Pathogenic
0.30
D
BayesDel_noAF
Pathogenic
0.19
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.58
D;.;.;.
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.83
T;D;D;D
M_CAP
Uncertain
0.18
D
MetaRNN
Pathogenic
0.98
D;D;D;D
MetaSVM
Pathogenic
0.84
D
MutationAssessor
Pathogenic
2.9
M;.;M;M
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-3.8
D;D;D;D
REVEL
Pathogenic
0.74
Sift
Uncertain
0.016
D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;.
Polyphen
1.0
D;.;D;D
Vest4
0.79
MutPred
0.90
Gain of glycosylation at S203 (P = 0.0571);Gain of glycosylation at S203 (P = 0.0571);Gain of glycosylation at S203 (P = 0.0571);Gain of glycosylation at S203 (P = 0.0571);
MVP
0.92
MPC
1.2
ClinPred
0.98
D
GERP RS
4.7
Varity_R
0.76
gMVP
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs281875298; hg19: chr9-136291386; API