rs3094374

chr9-133458126-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0700

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]

ACMG classification

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	UniProt
ADAMTS13	NM_139027.6	c.3909+32T>C		intron_variant		ENST00000355699.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS13	ENST00000355699.7	c.3909+32T>C		intron_variant		1	NM_139027.6	A2

Frequencies

GnomAD3 genomes AF: 0.0597 AC: 9088 AN: 152174 Hom.: 365 Cov.: 32

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

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.: 32 AF XY: 0.0791 AC XY: 57319 AN XY: 724362

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.: 32 AF XY: 0.0586 AC XY: 4364 AN XY: 74466

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.: 89

Bravo AF: 0.0558

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 17, 2020

This variant is associated with the following publications: (PMID: 25242241) -

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

Other links and lift over

dbSNP: rs3094374; hg19: chr9-136323248; COSMIC: COSV52470014; COSMIC: COSV52470014;