Variant 9-133430112-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

ADAMTS13 (HGNC:):

ADAMTS13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 262455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133430112-C-T is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS13	NM_139027.6 linkuse as main transcript	c.987+11C>T		intron_variant		ENST00000355699.7	NP_620596.2	Q76LX8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7 linkuse as main transcript	c.987+11C>T		intron_variant		1	NM_139027.6	ENSP00000347927.2		Q76LX8-2

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

GnomAD3 exomes

AF:

0.0850

AC:

15251

AN:

179412

Hom.:

828

AF XY:

0.0866

AC XY:

8589

AN XY:

99150

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 SAS exome

AF:

0.0420

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

Gnomad4 AFR exome

AF:

0.0375

Gnomad4 AMR exome

AF:

0.0497

Gnomad4 ASJ exome

AF:

0.0913

Gnomad4 EAS exome

AF:

0.000130

Gnomad4 SAS exome

AF:

0.0416

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.0976

GnomAD4 genome

AF:

0.0891

AC:

13574

AN:

152306

Hom.:

741

Cov.:

AF XY:

0.0891

AC XY:

6633

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0407

Gnomad4 AMR

AF:

0.0720

Gnomad4 ASJ

AF:

0.0979

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0377

Gnomad4 FIN

AF:

0.129

Gnomad4 NFE

AF:

0.126

Gnomad4 OTH

AF:

0.0855

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 17, 2020	This variant is associated with the following publications: (PMID: 25242241) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Upshaw-Schulman syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.9

DANN

Benign

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over