rs34054981

Variant names:

• chr9-133426241-C-T
• rs34054981
• NM_139027.6:c.582C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_139027.6(ADAMTS13):​c.582C>T​(p.Gly194Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0743 in 1,613,308 control chromosomes in the GnomAD database, including 5,200 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 (337 hom., cov: 33)
  • Exomes 𝑓: 0.076 (4863 hom.)
• Consequence: ADAMTS13 NM_139027.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.47
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• congenital thrombotic thrombocytopenic purpura

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 9-133426241-C-T is Benign according to our data. Variant chr9-133426241-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.087 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS13	NM_139027.6	c.582C>T	p.Gly194Gly	synonymous_variant	Exon 6 of 29	ENST00000355699.7	NP_620596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7	c.582C>T	p.Gly194Gly	synonymous_variant	Exon 6 of 29	1	NM_139027.6	ENSP00000347927.2

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 8508 AN: 152208 Hom.: 338 Cov.: 33

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.0471

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.0554

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0889

Gnomad OTH AF: 0.0578

GnomAD2 exomes AF: 0.0579 AC: 14510 AN: 250722 AF XY: 0.0585

Gnomad AFR exome AF: 0.0146

Gnomad AMR exome AF: 0.0321

Gnomad ASJ exome AF: 0.0706

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0560

Gnomad NFE exome AF: 0.0900

Gnomad OTH exome AF: 0.0645

GnomAD4 exome AF: 0.0763 AC: 111445 AN: 1460982 Hom.: 4863 Cov.: 37 AF XY: 0.0745 AC XY: 54143 AN XY: 726846

African (AFR) AF: 0.0125 AC: 418 AN: 33480

American (AMR) AF: 0.0335 AC: 1497 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 1813 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0212 AC: 1829 AN: 86258

European-Finnish (FIN) AF: 0.0565 AC: 2968 AN: 52540

Middle Eastern (MID) AF: 0.0595 AC: 343 AN: 5768

European-Non Finnish (NFE) AF: 0.0886 AC: 98501 AN: 1111992

Other (OTH) AF: 0.0674 AC: 4073 AN: 60386

GnomAD4 genome AF: 0.0558 AC: 8504 AN: 152326 Hom.: 337 Cov.: 33 AF XY: 0.0548 AC XY: 4079 AN XY: 74476

African (AFR) AF: 0.0155 AC: 643 AN: 41584

American (AMR) AF: 0.0472 AC: 722 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 254 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0213 AC: 103 AN: 4828

European-Finnish (FIN) AF: 0.0554 AC: 588 AN: 10612

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0889 AC: 6047 AN: 68022

Other (OTH) AF: 0.0568 AC: 120 AN: 2114

Alfa AF: 0.0768 Hom.: 869

Bravo AF: 0.0540

Asia WGS AF: 0.0150 AC: 53 AN: 3478

EpiCase AF: 0.0857

EpiControl AF: 0.0874

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Upshaw-Schulman syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.1
DANN	Benign	0.74
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34054981; hg19: chr9-136291361; COSMIC: COSV63022376;