rs28375042

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_139027.6(ADAMTS13):​c.1451G>A​(p.Arg484Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

ADAMTS13
NM_139027.6 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.59
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 Uncertain_significance. Variant got 2 ACMG points.

PM1
In a region_of_interest Cysteine-rich (size 116) in uniprot entity ATS13_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_139027.6
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18658155).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADAMTS13NM_139027.6 linkuse as main transcriptc.1451G>A p.Arg484Lys missense_variant 13/29 ENST00000355699.7 NP_620596.2 Q76LX8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADAMTS13ENST00000355699.7 linkuse as main transcriptc.1451G>A p.Arg484Lys missense_variant 13/291 NM_139027.6 ENSP00000347927.2 Q76LX8-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
19
DANN
Benign
0.94
DEOGEN2
Benign
0.060
T;T;.;.
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.22
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.69
T;T;T;T
M_CAP
Benign
0.0084
T
MetaRNN
Benign
0.19
T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
-0.47
N;.;N;.
PrimateAI
Benign
0.37
T
PROVEAN
Benign
0.080
N;.;N;N
REVEL
Benign
0.13
Sift
Benign
0.80
T;.;T;T
Sift4G
Benign
0.51
T;T;T;.
Polyphen
0.019
B;.;B;B
Vest4
0.17
MutPred
0.55
Gain of methylation at R484 (P = 0.0046);.;Gain of methylation at R484 (P = 0.0046);.;
MVP
0.79
MPC
0.34
ClinPred
0.34
T
GERP RS
4.4
Varity_R
0.32
gMVP
0.65

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: rs28375042; hg19: chr9-136302884; API