rs28503257

Positions:

chr9-133454467-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_139027.6(ADAMTS13):c.3097G>A(p.Ala1033Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0367 in 1,613,558 control chromosomes in the GnomAD database, including 1,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 107 hom., cov: 33)

Exomes 𝑓: 0.037 ( 1233 hom. )

Consequence

ADAMTS13
NM_139027.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.99

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=0.0028647482).

BP6

Variant 9-133454467-G-A is Benign according to our data. Variant chr9-133454467-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133454467-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0303 (4618/152356) while in subpopulation NFE AF= 0.0402 (2737/68026). AF 95% confidence interval is 0.039. There are 107 homozygotes in gnomad4. There are 2341 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 107 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS13	NM_139027.6 linkuse as main transcript	c.3097G>A	p.Ala1033Thr	missense_variant	24/29	ENST00000355699.7	NP_620596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7 linkuse as main transcript	c.3097G>A	p.Ala1033Thr	missense_variant	24/29	1	NM_139027.6	ENSP00000347927	A2	Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.0303

AC:

4616

AN:

152238

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.0224

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0727

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0402

Gnomad OTH

AF:

0.0272

GnomAD3 exomes

AF:

0.0308

AC:

7706

AN:

250526

Hom.:

165

AF XY:

0.0318

AC XY:

4310

AN XY:

135694

show subpopulations

Gnomad AFR exome

AF:

0.00869

Gnomad AMR exome

AF:

0.0148

Gnomad ASJ exome

AF:

0.0222

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0202

Gnomad FIN exome

AF:

0.0671

Gnomad NFE exome

AF:

0.0404

Gnomad OTH exome

AF:

0.0323

GnomAD4 exome

AF:

0.0373

AC:

54545

AN:

1461202

Hom.:

1233

Cov.:

AF XY:

0.0369

AC XY:

26825

AN XY:

726930

show subpopulations

Gnomad4 AFR exome

AF:

0.00821

Gnomad4 AMR exome

AF:

0.0148

Gnomad4 ASJ exome

AF:

0.0219

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0210

Gnomad4 FIN exome

AF:

0.0657

Gnomad4 NFE exome

AF:

0.0410

Gnomad4 OTH exome

AF:

0.0322

GnomAD4 genome

AF:

0.0303

AC:

4618

AN:

152356

Hom.:

107

Cov.:

AF XY:

0.0314

AC XY:

2341

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0104

Gnomad4 AMR

AF:

0.0223

Gnomad4 ASJ

AF:

0.0236

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.0727

Gnomad4 NFE

AF:

0.0402

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0351

Hom.:

153

Bravo

AF:

0.0253

TwinsUK

AF:

0.0378

AC:

140

ALSPAC

AF:

0.0428

AC:

165

ESP6500AA

AF:

0.00953

AC:

ESP6500EA

AF:

0.0400

AC:

344

ExAC

AF:

0.0317

AC:

3843

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0381

EpiControl

AF:

0.0372

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2020	This variant is associated with the following publications: (PMID: 22768050) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Upshaw-Schulman syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.060

T;.;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.66

T;T;T

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Pathogenic

3.0

M;M;.

MutationTaster

Benign

0.90

D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.18

T;T;T

Sift4G

Uncertain

0.0070

D;D;.

Polyphen

1.0

D;D;D

Vest4

0.22

MPC

1.1

ClinPred

0.059

GERP RS

5.6

Varity_R

0.24

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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