Variant rs28571612 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.354G>A(p.Pro118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 1,613,360 control chromosomes in the GnomAD database, including 4,962 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 321 hom., cov: 32)

Exomes 𝑓: 0.074 ( 4641 hom. )

Consequence

ADAMTS13
NM_139027.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.01

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 9-133425552-G-A is Benign according to our data. Variant chr9-133425552-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0848 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.354G>A	p.Pro118=	synonymous_variant	4/29	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.354G>A	p.Pro118=	synonymous_variant	4/29	1	NM_139027.6	ENSP00000347927	A2	Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.0549

AC:

8357

AN:

152140

Hom.:

321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0476

Gnomad ASJ

AF:

0.0711

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0199

Gnomad FIN

AF:

0.0560

Gnomad MID

AF:

0.0573

Gnomad NFE

AF:

0.0867

Gnomad OTH

AF:

0.0585

GnomAD3 exomes

AF:

0.0568

AC:

14169

AN:

249508

Hom.:

579

AF XY:

0.0572

AC XY:

7740

AN XY:

135240

show subpopulations

Gnomad AFR exome

AF:

0.0146

Gnomad AMR exome

AF:

0.0328

Gnomad ASJ exome

AF:

0.0692

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0202

Gnomad FIN exome

AF:

0.0568

Gnomad NFE exome

AF:

0.0879

Gnomad OTH exome

AF:

0.0636

GnomAD4 exome

AF:

0.0743

AC:

108616

AN:

1461102

Hom.:

4641

Cov.:

AF XY:

0.0726

AC XY:

52734

AN XY:

726838

show subpopulations

Gnomad4 AFR exome

AF:

0.0122

Gnomad4 AMR exome

AF:

0.0342

Gnomad4 ASJ exome

AF:

0.0678

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0203

Gnomad4 FIN exome

AF:

0.0566

Gnomad4 NFE exome

AF:

0.0862

Gnomad4 OTH exome

AF:

0.0659

GnomAD4 genome

AF:

0.0549

AC:

8356

AN:

152258

Hom.:

321

Cov.:

AF XY:

0.0540

AC XY:

4017

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0152

Gnomad4 AMR

AF:

0.0476

Gnomad4 ASJ

AF:

0.0711

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0201

Gnomad4 FIN

AF:

0.0560

Gnomad4 NFE

AF:

0.0866

Gnomad4 OTH

AF:

0.0579

Alfa

AF:

0.0766

Hom.:

525

Bravo

AF:

0.0531

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0828

EpiControl

AF:

0.0842

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	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 27, 2020	This variant is associated with the following publications: (PMID: 31731663) -

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

-0.80

CADD

Benign

1.9

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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