Variant rs1055432 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_139027.6(ADAMTS13):c.4053C>A(p.Thr1351=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,611,808 control chromosomes in the GnomAD database, including 94,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6084 hom., cov: 32)

Exomes 𝑓: 0.34 ( 88272 hom. )

Consequence

ADAMTS13
NM_139027.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:5

Conservation

PhyloP100: 0.135

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 9-133459117-C-A is Benign according to our data. Variant chr9-133459117-C-A is described in ClinVar as [Benign]. Clinvar id is 262450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133459117-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.135 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.35 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.4053C>A	p.Thr1351=	synonymous_variant	29/29	ENST00000355699.7	NP_620596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7 linkuse as main transcript	c.4053C>A	p.Thr1351=	synonymous_variant	29/29	1	NM_139027.6	ENSP00000347927	A2	Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38544

AN:

151778

Hom.:

6079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0710

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.345

Gnomad OTH

AF:

0.237

GnomAD3 exomes

AF:

0.312

AC:

77425

AN:

248506

Hom.:

13091

AF XY:

0.316

AC XY:

42575

AN XY:

134790

show subpopulations

Gnomad AFR exome

AF:

0.0671

Gnomad AMR exome

AF:

0.339

Gnomad ASJ exome

AF:

0.249

Gnomad EAS exome

AF:

0.179

Gnomad SAS exome

AF:

0.357

Gnomad FIN exome

AF:

0.349

Gnomad NFE exome

AF:

0.346

Gnomad OTH exome

AF:

0.303

GnomAD4 exome

AF:

0.341

AC:

498385

AN:

1459912

Hom.:

88272

Cov.:

AF XY:

0.342

AC XY:

248228

AN XY:

726162

show subpopulations

Gnomad4 AFR exome

AF:

0.0607

Gnomad4 AMR exome

AF:

0.335

Gnomad4 ASJ exome

AF:

0.255

Gnomad4 EAS exome

AF:

0.178

Gnomad4 SAS exome

AF:

0.359

Gnomad4 FIN exome

AF:

0.359

Gnomad4 NFE exome

AF:

0.358

Gnomad4 OTH exome

AF:

0.313

GnomAD4 genome

AF:

0.254

AC:

38565

AN:

151896

Hom.:

6084

Cov.:

AF XY:

0.254

AC XY:

18863

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.0710

Gnomad4 AMR

AF:

0.272

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.189

Gnomad4 SAS

AF:

0.364

Gnomad4 FIN

AF:

0.349

Gnomad4 NFE

AF:

0.345

Gnomad4 OTH

AF:

0.237

Alfa

AF:

0.307

Hom.:

9019

Bravo

AF:

0.238

Asia WGS

AF:

0.290

AC:

1007

AN:

3478

EpiCase

AF:

0.329

EpiControl

AF:

0.322

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:5

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 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Upshaw-Schulman syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 18, 2021	- -

Three Vessel Coronary Disease

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

2.2

DANN

Benign

0.79

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