Variant 9-133445787-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.2699C>T(p.Ala900Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 1,596,052 control chromosomes in the GnomAD database, including 8,223 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 873 hom., cov: 32)

Exomes 𝑓: 0.096 ( 7350 hom. )

Consequence

ADAMTS13
NM_139027.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.69

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:

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 (MetaRNN=0.0023660362).

BP6

Variant 9-133445787-C-T is Benign according to our data. Variant chr9-133445787-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS13	NM_139027.6 link	c.2699C>T	p.Ala900Val	missense_variant	21/29	ENST00000355699.7	NP_620596.2	Q76LX8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7 link	c.2699C>T	p.Ala900Val	missense_variant	21/29	1	NM_139027.6	ENSP00000347927.2		Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15796

AN:

152040

Hom.:

870

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.0736

Gnomad ASJ

AF:

0.0516

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.0806

AC:

19610

AN:

243220

Hom.:

981

AF XY:

0.0789

AC XY:

10413

AN XY:

132018

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.0498

Gnomad ASJ exome

AF:

0.0503

Gnomad EAS exome

AF:

0.000328

Gnomad SAS exome

AF:

0.0302

Gnomad FIN exome

AF:

0.116

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.0907

GnomAD4 exome

AF:

0.0962

AC:

138955

AN:

1443894

Hom.:

7350

Cov.:

AF XY:

0.0940

AC XY:

67203

AN XY:

714746

show subpopulations

Gnomad4 AFR exome

AF:

0.143

Gnomad4 AMR exome

AF:

0.0518

Gnomad4 ASJ exome

AF:

0.0503

Gnomad4 EAS exome

AF:

0.000280

Gnomad4 SAS exome

AF:

0.0312

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.106

Gnomad4 OTH exome

AF:

0.0909

GnomAD4 genome

AF:

0.104

AC:

15820

AN:

152158

Hom.:

873

Cov.:

AF XY:

0.103

AC XY:

7637

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.0737

Gnomad4 ASJ

AF:

0.0516

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.0263

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.0991

Alfa

AF:

0.102

Hom.:

641

Bravo

AF:

0.104

TwinsUK

AF:

0.0982

AC:

364

ALSPAC

AF:

0.112

AC:

431

ESP6500AA

AF:

0.132

AC:

582

ESP6500EA

AF:

0.103

AC:

887

ExAC

AF:

0.0839

AC:

10179

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

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	This variant is associated with the following publications: (PMID: 19427680, 22768050) -

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

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.5

DANN

Benign

0.16

DEOGEN2

Benign

0.033

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.00025

LIST_S2

Benign

0.22

T;T;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-2.3

N;N;.

PrimateAI

Benign

0.29

PROVEAN

Benign

0.88

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.44

T;T;T

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0

B;B;B

Vest4

0.019

MPC

0.33

ClinPred

0.00082

GERP RS

4.5

Varity_R

0.025

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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