Variant 9-133458126-T-C 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.3909+32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 1,608,938 control chromosomes in the GnomAD database, including 5,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 364 hom., cov: 32)

Exomes 𝑓: 0.080 ( 5256 hom. )

Consequence

ADAMTS13
NM_139027.6 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0700

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 9-133458126-T-C is Benign according to our data. Variant chr9-133458126-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 262449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0883 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.3909+32T>C		intron_variant		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.3909+32T>C		intron_variant		1	NM_139027.6	ENSP00000347927.2		Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.0597

AC:

9088

AN:

152174

Hom.:

365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0172

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0567

Gnomad ASJ

AF:

0.0412

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0232

Gnomad FIN

AF:

0.0836

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0902

Gnomad OTH

AF:

0.0733

GnomAD3 exomes

AF:

0.0613

AC:

14805

AN:

241340

Hom.:

579

AF XY:

0.0625

AC XY:

8184

AN XY:

130930

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.0402

Gnomad ASJ exome

AF:

0.0468

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.0269

Gnomad FIN exome

AF:

0.0930

Gnomad NFE exome

AF:

0.0886

Gnomad OTH exome

AF:

0.0782

GnomAD4 exome

AF:

0.0803

AC:

116943

AN:

1456646

Hom.:

5256

Cov.:

AF XY:

0.0791

AC XY:

57319

AN XY:

724362

show subpopulations

Gnomad4 AFR exome

AF:

0.0140

Gnomad4 AMR exome

AF:

0.0413

Gnomad4 ASJ exome

AF:

0.0447

Gnomad4 EAS exome

AF:

0.000253

Gnomad4 SAS exome

AF:

0.0269

Gnomad4 FIN exome

AF:

0.0905

Gnomad4 NFE exome

AF:

0.0914

Gnomad4 OTH exome

AF:

0.0752

GnomAD4 genome

AF:

0.0597

AC:

9088

AN:

152292

Hom.:

364

Cov.:

AF XY:

0.0586

AC XY:

4364

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0172

Gnomad4 AMR

AF:

0.0566

Gnomad4 ASJ

AF:

0.0412

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0236

Gnomad4 FIN

AF:

0.0836

Gnomad4 NFE

AF:

0.0902

Gnomad4 OTH

AF:

0.0720

Alfa

AF:

0.0688

Hom.:

Bravo

AF:

0.0558

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 17, 2020	This variant is associated with the following publications: (PMID: 25242241) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely 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

-0.90

CADD

Benign

5.8

DANN

Benign

0.63

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