9-133422462-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139027.6(ADAMTS13):c.19C>T(p.Arg7Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,613,772 control chromosomes in the GnomAD database, including 11,180 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 802 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10378 hom. )

Consequence

ADAMTS13
NM_139027.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.39

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]

ADAMTS13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015433729).

BP6

Variant 9-133422462-C-T is Benign according to our data. Variant chr9-133422462-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133422462-C-T is described in Lovd as [Benign]. Variant chr9-133422462-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS13	NM_139027.6 link	c.19C>T	p.Arg7Trp	missense_variant	Exon 1 of 29	ENST00000355699.7	NP_620596.2	Q76LX8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7 link	c.19C>T	p.Arg7Trp	missense_variant	Exon 1 of 29	1	NM_139027.6	ENSP00000347927.2		Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.0928

AC:

14117

AN:

152150

Hom.:

802

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0482

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.0759

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.0383

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.0910

GnomAD3 exomes

AF:

0.0906

AC:

22741

AN:

251060

Hom.:

1352

AF XY:

0.0918

AC XY:

12463

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.0454

Gnomad AMR exome

AF:

0.0513

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.00217

Gnomad SAS exome

AF:

0.0426

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.129

Gnomad OTH exome

AF:

0.0996

GnomAD4 exome

AF:

0.113

AC:

165459

AN:

1461504

Hom.:

10378

Cov.:

AF XY:

0.111

AC XY:

80750

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.0454

Gnomad4 AMR exome

AF:

0.0530

Gnomad4 ASJ exome

AF:

0.0994

Gnomad4 EAS exome

AF:

0.00237

Gnomad4 SAS exome

AF:

0.0429

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.102

GnomAD4 genome

AF:

0.0928

AC:

14123

AN:

152268

Hom.:

802

Cov.:

AF XY:

0.0924

AC XY:

6881

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0483

Gnomad4 AMR

AF:

0.0759

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.00290

Gnomad4 SAS

AF:

0.0384

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.128

Gnomad4 OTH

AF:

0.0896

Alfa

AF:

0.112

Hom.:

2003

Bravo

AF:

0.0882

TwinsUK

AF:

0.133

AC:

492

ALSPAC

AF:

0.139

AC:

534

ESP6500AA

AF:

0.0517

AC:

228

ESP6500EA

AF:

0.125

AC:

1071

ExAC

AF:

0.0938

AC:

11390

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.125

EpiControl

AF:

0.125

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 12614216, 16160007, 32531546) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Upshaw-Schulman syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.38

DANN

Benign

0.68

DEOGEN2

Benign

0.064

T;.;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.66

T;T;T;T

MetaRNN

Benign

0.0015

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.75

N;.;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.48

N;N;N;N

REVEL

Benign

0.056

Sift

Benign

0.090

T;T;T;T

Sift4G

Benign

0.10

T;T;T;.

Polyphen

0.0

B;.;B;B

Vest4

0.054

MPC

0.35

ClinPred

0.00086

GERP RS

-6.5

Varity_R

0.054

gMVP

0.39

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over