9-133430112-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139027.6(ADAMTS13):c.987+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,571,394 control chromosomes in the GnomAD database, including 10,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 741 hom., cov: 30)

Exomes 𝑓: 0.11 ( 9786 hom. )

Consequence

ADAMTS13
NM_139027.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.384

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 9-133430112-C-T is Benign according to our data. Variant chr9-133430112-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139027.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADAMTS13	NM_139027.6	MANE Select	c.987+11C>T	intron	N/A	NP_620596.2
ADAMTS13	NM_139025.5		c.987+11C>T	intron	N/A	NP_620594.1
ADAMTS13	NM_139026.6		c.894+11C>T	intron	N/A	NP_620595.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADAMTS13	ENST00000355699.7	TSL:1 MANE Select	c.987+11C>T	intron	N/A	ENSP00000347927.2
ADAMTS13	ENST00000371929.7	TSL:1	c.987+11C>T	intron	N/A	ENSP00000360997.3
ADAMTS13	ENST00000356589.6	TSL:1	c.894+11C>T	intron	N/A	ENSP00000348997.2

Frequencies

GnomAD3 genomes

AF:

0.0892

AC:

13575

AN:

152188

Hom.:

742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0407

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.0721

Gnomad ASJ

AF:

0.0979

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0376

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.0869

GnomAD2 exomes

AF:

0.0850

AC:

15251

AN:

179412

AF XY:

0.0866

show subpopulations

Gnomad AFR exome

AF:

0.0393

Gnomad AMR exome

AF:

0.0493

Gnomad ASJ exome

AF:

0.0942

Gnomad EAS exome

AF:

0.000270

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.130

Gnomad OTH exome

AF:

0.0935

GnomAD4 exome

AF:

0.111

AC:

157759

AN:

1419088

Hom.:

9786

Cov.:

AF XY:

0.109

AC XY:

76635

AN XY:

703796

show subpopulations

African (AFR)

AF:

0.0375

AC:

1235

AN:

32944

American (AMR)

AF:

0.0497

AC:

2053

AN:

41274

Ashkenazi Jewish (ASJ)

AF:

0.0913

AC:

2334

AN:

25558

East Asian (EAS)

AF:

0.000130

AC:

AN:

38368

South Asian (SAS)

AF:

0.0416

AC:

3436

AN:

82656

European-Finnish (FIN)

AF:

0.124

AC:

4696

AN:

37862

Middle Eastern (MID)

AF:

0.0930

AC:

529

AN:

5688

European-Non Finnish (NFE)

AF:

0.126

AC:

137713

AN:

1095744

Other (OTH)

AF:

0.0976

AC:

5758

AN:

58994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

8492

16984

25475

33967

42459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4848

9696

14544

19392

24240

<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:

0.0891

AC:

13574

AN:

152306

Hom.:

741

Cov.:

AF XY:

0.0891

AC XY:

6633

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0407

AC:

1692

AN:

41570

American (AMR)

AF:

0.0720

AC:

1103

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0979

AC:

340

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.0377

AC:

182

AN:

4832

European-Finnish (FIN)

AF:

0.129

AC:

1373

AN:

10606

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.126

AC:

8559

AN:

68016

Other (OTH)

AF:

0.0855

AC:

181

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

621

1241

1862

2482

3103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<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:

0.107

Hom.:

188

Bravo

AF:

0.0833

Asia WGS

AF:

0.0240

AC:

AN:

3478

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 17, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 25242241)

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

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

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.9

(source)

DANN

Benign

0.85

PhyloP100

-0.38

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over