rs28571612

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_139027.6(ADAMTS13):c.354G>A(p.Pro118Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 1,613,360 control chromosomes in the GnomAD database, including 4,962 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 321 hom., cov: 32)

Exomes 𝑓: 0.074 ( 4641 hom. )

Consequence

ADAMTS13
NM_139027.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.01

Publications

15 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=-0.8).

BP6

Variant 9-133425552-G-A is Benign according to our data. Variant chr9-133425552-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS13	NM_139027.6 link	c.354G>A	p.Pro118Pro	synonymous_variant	Exon 4 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.354G>A	p.Pro118Pro	synonymous_variant	Exon 4 of 29	1	NM_139027.6	ENSP00000347927.2

Frequencies

GnomAD3 genomes

AF:

0.0549

AC:

8357

AN:

152140

Hom.:

321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0476

Gnomad ASJ

AF:

0.0711

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0199

Gnomad FIN

AF:

0.0560

Gnomad MID

AF:

0.0573

Gnomad NFE

AF:

0.0867

Gnomad OTH

AF:

0.0585

GnomAD2 exomes

AF:

0.0568

AC:

14169

AN:

249508

AF XY:

0.0572

show subpopulations

Gnomad AFR exome

AF:

0.0146

Gnomad AMR exome

AF:

0.0328

Gnomad ASJ exome

AF:

0.0692

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0568

Gnomad NFE exome

AF:

0.0879

Gnomad OTH exome

AF:

0.0636

GnomAD4 exome

AF:

0.0743

AC:

108616

AN:

1461102

Hom.:

4641

Cov.:

AF XY:

0.0726

AC XY:

52734

AN XY:

726838

show subpopulations

African (AFR)

AF:

0.0122

AC:

409

AN:

33480

American (AMR)

AF:

0.0342

AC:

1530

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0678

AC:

1772

AN:

26128

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39696

South Asian (SAS)

AF:

0.0203

AC:

1746

AN:

86198

European-Finnish (FIN)

AF:

0.0566

AC:

2996

AN:

52968

Middle Eastern (MID)

AF:

0.0563

AC:

324

AN:

5760

European-Non Finnish (NFE)

AF:

0.0862

AC:

95855

AN:

1111800

Other (OTH)

AF:

0.0659

AC:

3981

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

5233

10466

15699

20932

26165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3406

6812

10218

13624

17030

<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:

0.0549

AC:

8356

AN:

152258

Hom.:

321

Cov.:

AF XY:

0.0540

AC XY:

4017

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0152

AC:

632

AN:

41566

American (AMR)

AF:

0.0476

AC:

728

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0711

AC:

247

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.0201

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0560

AC:

594

AN:

10606

Middle Eastern (MID)

AF:

0.0582

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0866

AC:

5892

AN:

68008

Other (OTH)

AF:

0.0579

AC:

122

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

406

813

1219

1626

2032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0702

Hom.:

641

Bravo

AF:

0.0531

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0828

EpiControl

AF:

0.0842

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 27, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 31731663) -

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

-0.80

CADD

Benign

1.9

(source)

DANN

Benign

0.72

PhyloP100

-4.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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