Variant rs34934621 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.3108G>A(p.Ser1036Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 1,613,288 control chromosomes in the GnomAD database, including 1,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 106 hom., cov: 33)

Exomes 𝑓: 0.045 ( 1681 hom. )

Consequence

ADAMTS13
NM_139027.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.43

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 9-133454478-G-A is Benign according to our data. Variant chr9-133454478-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133454478-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.43 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0517 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.3108G>A	p.Ser1036Ser	synonymous_variant	24/29	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.3108G>A	p.Ser1036Ser	synonymous_variant	24/29	1	NM_139027.6	ENSP00000347927.2		Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.0327

AC:

4972

AN:

152212

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.0373

Gnomad ASJ

AF:

0.0527

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.0197

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0499

Gnomad OTH

AF:

0.0407

GnomAD3 exomes

AF:

0.0327

AC:

8195

AN:

250278

Hom.:

201

AF XY:

0.0335

AC XY:

4549

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.00925

Gnomad AMR exome

AF:

0.0227

Gnomad ASJ exome

AF:

0.0528

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0151

Gnomad FIN exome

AF:

0.0177

Gnomad NFE exome

AF:

0.0499

Gnomad OTH exome

AF:

0.0408

GnomAD4 exome

AF:

0.0449

AC:

65548

AN:

1460958

Hom.:

1681

Cov.:

AF XY:

0.0438

AC XY:

31866

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.00824

Gnomad4 AMR exome

AF:

0.0241

Gnomad4 ASJ exome

AF:

0.0507

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0151

Gnomad4 FIN exome

AF:

0.0170

Gnomad4 NFE exome

AF:

0.0521

Gnomad4 OTH exome

AF:

0.0412

GnomAD4 genome

AF:

0.0326

AC:

4970

AN:

152330

Hom.:

106

Cov.:

AF XY:

0.0321

AC XY:

2393

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.0373

Gnomad4 ASJ

AF:

0.0527

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0147

Gnomad4 FIN

AF:

0.0197

Gnomad4 NFE

AF:

0.0499

Gnomad4 OTH

AF:

0.0403

Alfa

AF:

0.0425

Hom.:

Bravo

AF:

0.0338

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.0523

EpiControl

AF:

0.0557

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
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

-0.78

CADD

Benign

0.22

DANN

Benign

0.64

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