dbSNP rs3124768: ADAMTS13:p.Thr572Thr (chr9-133439376-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_139027.6(ADAMTS13):c.1716G>A(p.Thr572Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,611,636 control chromosomes in the GnomAD database, including 255,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.57 ( 25101 hom., cov: 33)

Exomes 𝑓: 0.56 ( 230424 hom. )

Consequence

ADAMTS13
NM_139027.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.99

Publications

42 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 9-133439376-G-A is Benign according to our data. Variant chr9-133439376-G-A is described in ClinVar as [Benign]. Clinvar id is 769359.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-5.99 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS13	NM_139027.6 link	c.1716G>A	p.Thr572Thr	synonymous_variant	Exon 15 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.1716G>A	p.Thr572Thr	synonymous_variant	Exon 15 of 29	1	NM_139027.6	ENSP00000347927.2		Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.565

AC:

85905

AN:

152060

Hom.:

25067

Cov.:

show subpopulations

Gnomad AFR

AF:

0.639

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.633

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.571

Gnomad OTH

AF:

0.525

GnomAD4 exome

AF:

0.556

AC:

810938

AN:

1459458

Hom.:

230424

Cov.:

AF XY:

0.553

AC XY:

401801

AN XY:

726282

show subpopulations

African (AFR)

AF:

0.642

AC:

21477

AN:

33442

American (AMR)

AF:

0.503

AC:

22488

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

9730

AN:

26100

East Asian (EAS)

AF:

0.191

AC:

7562

AN:

39666

South Asian (SAS)

AF:

0.490

AC:

42228

AN:

86198

European-Finnish (FIN)

AF:

0.642

AC:

34259

AN:

53384

Middle Eastern (MID)

AF:

0.470

AC:

2708

AN:

5760

European-Non Finnish (NFE)

AF:

0.575

AC:

638411

AN:

1109908

Other (OTH)

AF:

0.532

AC:

32075

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

Heterozygous variant carriers

20440

40881

61321

81762

102202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.565

AC:

85982

AN:

152178

Hom.:

25101

Cov.:

AF XY:

0.564

AC XY:

41978

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.639

AC:

26508

AN:

41510

American (AMR)

AF:

0.503

AC:

7701

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

1290

AN:

3472

East Asian (EAS)

AF:

0.192

AC:

997

AN:

5180

South Asian (SAS)

AF:

0.479

AC:

2306

AN:

4816

European-Finnish (FIN)

AF:

0.633

AC:

6696

AN:

10586

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.571

AC:

38857

AN:

68000

Other (OTH)

AF:

0.520

AC:

1098

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1901

3801

5702

7602

9503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.561

Hom.:

89888

Bravo

AF:

0.553

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-1.0

CADD

Benign

0.037

(source)

PhyloP100

-6.0

Splicing

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

Publications

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rs3124768

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