rs1055432

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_139027.6(ADAMTS13):c.4053C>A(p.Thr1351Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,611,808 control chromosomes in the GnomAD database, including 94,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1351T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.25 ( 6084 hom., cov: 32)

Exomes 𝑓: 0.34 ( 88272 hom. )

Consequence

ADAMTS13
NM_139027.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:5

Conservation

PhyloP100: 0.135

Publications

25 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 9-133459117-C-A is Benign according to our data. Variant chr9-133459117-C-A is described in ClinVar as Benign. ClinVar VariationId is 262450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.135 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS13	NM_139027.6 link	c.4053C>A	p.Thr1351Thr	synonymous_variant	Exon 29 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.4053C>A	p.Thr1351Thr	synonymous_variant	Exon 29 of 29	1	NM_139027.6	ENSP00000347927.2		Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38544

AN:

151778

Hom.:

6079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0710

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.345

Gnomad OTH

AF:

0.237

GnomAD2 exomes

AF:

0.312

AC:

77425

AN:

248506

AF XY:

0.316

show subpopulations

Gnomad AFR exome

AF:

0.0671

Gnomad AMR exome

AF:

0.339

Gnomad ASJ exome

AF:

0.249

Gnomad EAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.349

Gnomad NFE exome

AF:

0.346

Gnomad OTH exome

AF:

0.303

GnomAD4 exome

AF:

0.341

AC:

498385

AN:

1459912

Hom.:

88272

Cov.:

AF XY:

0.342

AC XY:

248228

AN XY:

726162

show subpopulations

African (AFR)

AF:

0.0607

AC:

2032

AN:

33474

American (AMR)

AF:

0.335

AC:

14935

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

6651

AN:

26128

East Asian (EAS)

AF:

0.178

AC:

7060

AN:

39678

South Asian (SAS)

AF:

0.359

AC:

30955

AN:

86138

European-Finnish (FIN)

AF:

0.359

AC:

18834

AN:

52390

Middle Eastern (MID)

AF:

0.200

AC:

1150

AN:

5760

European-Non Finnish (NFE)

AF:

0.358

AC:

397885

AN:

1111414

Other (OTH)

AF:

0.313

AC:

18883

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

19088

38177

57265

76354

95442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12610

25220

37830

50440

63050

<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:

0.254

AC:

38565

AN:

151896

Hom.:

6084

Cov.:

AF XY:

0.254

AC XY:

18863

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.0710

AC:

2944

AN:

41466

American (AMR)

AF:

0.272

AC:

4153

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

863

AN:

3472

East Asian (EAS)

AF:

0.189

AC:

969

AN:

5140

South Asian (SAS)

AF:

0.364

AC:

1747

AN:

4800

European-Finnish (FIN)

AF:

0.349

AC:

3680

AN:

10556

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.345

AC:

23431

AN:

67884

Other (OTH)

AF:

0.237

AC:

501

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1353

2706

4060

5413

6766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.297

Hom.:

16842

Bravo

AF:

0.238

Asia WGS

AF:

0.290

AC:

1007

AN:

3478

EpiCase

AF:

0.329

EpiControl

AF:

0.322

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Upshaw-Schulman syndrome

Benign:2

Aug 18, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Three Vessel Coronary Disease

Uncertain:1

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: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

-0.31

CADD

Benign

2.2

(source)

DANN

Benign

0.79

PhyloP100

0.14

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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