rs28641026

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_139027.6(ADAMTS13):c.2910C>T(p.Val970Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0369 in 1,613,948 control chromosomes in the GnomAD database, including 1,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 104 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1240 hom. )

Consequence

ADAMTS13
NM_139027.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.14

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

congenital thrombotic thrombocytopenic purpura
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ADAMTS13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 9-133449831-C-T is Benign according to our data. Variant chr9-133449831-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.14 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0308 (4694/152198) while in subpopulation NFE AF = 0.0403 (2742/67996). AF 95% confidence interval is 0.0391. There are 104 homozygotes in GnomAd4. There are 2366 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 104 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS13	NM_139027.6 link	c.2910C>T	p.Val970Val	synonymous_variant	Exon 23 of 29	ENST00000355699.7	NP_620596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7 link	c.2910C>T	p.Val970Val	synonymous_variant	Exon 23 of 29	1	NM_139027.6	ENSP00000347927.2

Frequencies

GnomAD3 genomes

AF:

0.0309

AC:

4692

AN:

152080

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0117

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0188

Gnomad FIN

AF:

0.0723

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0403

Gnomad OTH

AF:

0.0283

GnomAD2 exomes

AF:

0.0313

AC:

7850

AN:

250634

AF XY:

0.0324

show subpopulations

Gnomad AFR exome

AF:

0.0100

Gnomad AMR exome

AF:

0.0150

Gnomad ASJ exome

AF:

0.0227

Gnomad EAS exome

AF:

0.000544

Gnomad FIN exome

AF:

0.0675

Gnomad NFE exome

AF:

0.0405

Gnomad OTH exome

AF:

0.0335

GnomAD4 exome

AF:

0.0376

AC:

54923

AN:

1461750

Hom.:

1240

Cov.:

AF XY:

0.0372

AC XY:

27065

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.00980

AC:

328

AN:

33480

American (AMR)

AF:

0.0149

AC:

667

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0222

AC:

581

AN:

26134

East Asian (EAS)

AF:

0.000327

AC:

AN:

39700

South Asian (SAS)

AF:

0.0229

AC:

1979

AN:

86252

European-Finnish (FIN)

AF:

0.0660

AC:

3520

AN:

53316

Middle Eastern (MID)

AF:

0.0333

AC:

192

AN:

5758

European-Non Finnish (NFE)

AF:

0.0411

AC:

45684

AN:

1112002

Other (OTH)

AF:

0.0324

AC:

1959

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

3265

6530

9796

13061

16326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1656

3312

4968

6624

8280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0308

AC:

4694

AN:

152198

Hom.:

104

Cov.:

AF XY:

0.0318

AC XY:

2366

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0117

AC:

488

AN:

41542

American (AMR)

AF:

0.0226

AC:

345

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.0186

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0723

AC:

766

AN:

10588

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0403

AC:

2742

AN:

67996

Other (OTH)

AF:

0.0280

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

240

480

719

959

1199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0311

Hom.:

Bravo

AF:

0.0258

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.0379

EpiControl

AF:

0.0370

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

- -

May 04, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 22768050) -

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

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.27

(source)

DANN

Benign

0.79

PhyloP100

-5.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over