Variant rs34054981 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_139027.6(ADAMTS13):c.582C>T(p.Gly194Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0743 in 1,613,308 control chromosomes in the GnomAD database, including 5,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 337 hom., cov: 33)

Exomes 𝑓: 0.076 ( 4863 hom. )

Consequence

ADAMTS13
NM_139027.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.47

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 9-133426241-C-T is Benign according to our data. Variant chr9-133426241-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133426241-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.47 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.087 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.582C>T	p.Gly194Gly	synonymous_variant	6/29	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.582C>T	p.Gly194Gly	synonymous_variant	6/29	1	NM_139027.6	ENSP00000347927.2		Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.0559

AC:

8508

AN:

152208

Hom.:

338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.00879

Gnomad AMR

AF:

0.0471

Gnomad ASJ

AF:

0.0732

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.0554

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0889

Gnomad OTH

AF:

0.0578

GnomAD3 exomes

AF:

0.0579

AC:

14510

AN:

250722

Hom.:

612

AF XY:

0.0585

AC XY:

7933

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.0146

Gnomad AMR exome

AF:

0.0321

Gnomad ASJ exome

AF:

0.0706

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0212

Gnomad FIN exome

AF:

0.0560

Gnomad NFE exome

AF:

0.0900

Gnomad OTH exome

AF:

0.0645

GnomAD4 exome

AF:

0.0763

AC:

111445

AN:

1460982

Hom.:

4863

Cov.:

AF XY:

0.0745

AC XY:

54143

AN XY:

726846

show subpopulations

Gnomad4 AFR exome

AF:

0.0125

Gnomad4 AMR exome

AF:

0.0335

Gnomad4 ASJ exome

AF:

0.0694

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0212

Gnomad4 FIN exome

AF:

0.0565

Gnomad4 NFE exome

AF:

0.0886

Gnomad4 OTH exome

AF:

0.0674

GnomAD4 genome

AF:

0.0558

AC:

8504

AN:

152326

Hom.:

337

Cov.:

AF XY:

0.0548

AC XY:

4079

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0155

Gnomad4 AMR

AF:

0.0472

Gnomad4 ASJ

AF:

0.0732

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0213

Gnomad4 FIN

AF:

0.0554

Gnomad4 NFE

AF:

0.0889

Gnomad4 OTH

AF:

0.0568

Alfa

AF:

0.0804

Hom.:

624

Bravo

AF:

0.0540

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0857

EpiControl

AF:

0.0874

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	Jun 09, 2021	- -
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

-0.73

CADD

Benign

5.1

DANN

Benign

0.74

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