rs34934621

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.3108G>A(p.Ser1036Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 1,613,288 control chromosomes in the GnomAD database, including 1,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 106 hom., cov: 33)

Exomes 𝑓: 0.045 ( 1681 hom. )

Consequence

ADAMTS13
NM_139027.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.43

Publications

5 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=-0.78).

BP6

Variant 9-133454478-G-A is Benign according to our data. Variant chr9-133454478-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.43 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS13	NM_139027.6 link	c.3108G>A	p.Ser1036Ser	synonymous_variant	Exon 24 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.3108G>A	p.Ser1036Ser	synonymous_variant	Exon 24 of 29	1	NM_139027.6	ENSP00000347927.2		Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.0327

AC:

4972

AN:

152212

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.0373

Gnomad ASJ

AF:

0.0527

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.0197

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0499

Gnomad OTH

AF:

0.0407

GnomAD2 exomes

AF:

0.0327

AC:

8195

AN:

250278

AF XY:

0.0335

show subpopulations

Gnomad AFR exome

AF:

0.00925

Gnomad AMR exome

AF:

0.0227

Gnomad ASJ exome

AF:

0.0528

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0177

Gnomad NFE exome

AF:

0.0499

Gnomad OTH exome

AF:

0.0408

GnomAD4 exome

AF:

0.0449

AC:

65548

AN:

1460958

Hom.:

1681

Cov.:

AF XY:

0.0438

AC XY:

31866

AN XY:

726822

show subpopulations

African (AFR)

AF:

0.00824

AC:

276

AN:

33476

American (AMR)

AF:

0.0241

AC:

1077

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0507

AC:

1325

AN:

26132

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0151

AC:

1301

AN:

86252

European-Finnish (FIN)

AF:

0.0170

AC:

892

AN:

52550

Middle Eastern (MID)

AF:

0.0491

AC:

283

AN:

5766

European-Non Finnish (NFE)

AF:

0.0521

AC:

57904

AN:

1111984

Other (OTH)

AF:

0.0412

AC:

2488

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

4324

8647

12971

17294

21618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2160

4320

6480

8640

10800

<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:

0.0326

AC:

4970

AN:

152330

Hom.:

106

Cov.:

AF XY:

0.0321

AC XY:

2393

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0101

AC:

418

AN:

41568

American (AMR)

AF:

0.0373

AC:

571

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0527

AC:

183

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.0147

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0197

AC:

209

AN:

10626

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0499

AC:

3394

AN:

68036

Other (OTH)

AF:

0.0403

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

267

534

802

1069

1336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0381

Hom.:

Bravo

AF:

0.0338

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.0523

EpiControl

AF:

0.0557

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 02, 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

- -

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

-0.78

CADD

Benign

0.22

(source)

DANN

Benign

0.64

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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