Variant rs36219245 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.686+4T>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 1,599,886 control chromosomes in the GnomAD database, including 5,192 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 ( 341 hom., cov: 33)

Exomes 𝑓: 0.077 ( 4851 hom. )

Consequence

ADAMTS13
NM_139027.6 splice_donor_region, intron

Scores

Splicing: ADA: 0.00008326

Clinical Significance

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

Conservation

PhyloP100: -1.13

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 9-133426349-T-G is Benign according to our data. Variant chr9-133426349-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 262453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133426349-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0873 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.686+4T>G		splice_donor_region_variant, intron_variant		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.686+4T>G		splice_donor_region_variant, intron_variant		1	NM_139027.6	ENSP00000347927	A2	Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.0561

AC:

8536

AN:

152082

Hom.:

342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.00879

Gnomad AMR

AF:

0.0474

Gnomad ASJ

AF:

0.0732

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.0565

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0892

Gnomad OTH

AF:

0.0578

GnomAD3 exomes

AF:

0.0580

AC:

13946

AN:

240260

Hom.:

585

AF XY:

0.0586

AC XY:

7664

AN XY:

130844

show subpopulations

Gnomad AFR exome

AF:

0.0147

Gnomad AMR exome

AF:

0.0321

Gnomad ASJ exome

AF:

0.0702

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0212

Gnomad FIN exome

AF:

0.0572

Gnomad NFE exome

AF:

0.0902

Gnomad OTH exome

AF:

0.0651

GnomAD4 exome

AF:

0.0767

AC:

111029

AN:

1447686

Hom.:

4851

Cov.:

AF XY:

0.0748

AC XY:

53910

AN XY:

720616

show subpopulations

Gnomad4 AFR exome

AF:

0.0126

Gnomad4 AMR exome

AF:

0.0335

Gnomad4 ASJ exome

AF:

0.0693

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0211

Gnomad4 FIN exome

AF:

0.0585

Gnomad4 NFE exome

AF:

0.0888

Gnomad4 OTH exome

AF:

0.0675

GnomAD4 genome

AF:

0.0561

AC:

8532

AN:

152200

Hom.:

341

Cov.:

AF XY:

0.0550

AC XY:

4092

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0155

Gnomad4 AMR

AF:

0.0474

Gnomad4 ASJ

AF:

0.0732

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0213

Gnomad4 FIN

AF:

0.0565

Gnomad4 NFE

AF:

0.0892

Gnomad4 OTH

AF:

0.0568

Alfa

AF:

0.0711

Hom.:

105

Bravo

AF:

0.0541

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0858

EpiControl

AF:

0.0875

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	GeneDx	Jun 09, 2021	This variant is associated with the following publications: (PMID: 26284228) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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

-0.85

CADD

Benign

5.6

DANN

Benign

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000083

dbscSNV1_RF

Benign

0.0020

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