rs35410697

Variant names:

• chr9-133424303-C-T
• rs35410697
• NM_139027.6:c.173-18C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_139027.6(ADAMTS13):​c.173-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0585 in 1,610,810 control chromosomes in the GnomAD database, including 3,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (228 hom., cov: 32)
  • Exomes 𝑓: 0.060 (3021 hom.)
• Consequence: ADAMTS13 NM_139027.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.520
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-133424303-C-T is Benign according to our data. Variant chr9-133424303-C-T is described in ClinVar as Benign. ClinVar VariationId is 262427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS13	NM_139027.6	c.173-18C>T		intron_variant	Intron 2 of 28	ENST00000355699.7	NP_620596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7	c.173-18C>T		intron_variant	Intron 2 of 28	1	NM_139027.6	ENSP00000347927.2

Frequencies

GnomAD3 genomes AF: 0.0449 AC: 6832 AN: 152100 Hom.: 229 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0403

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0711

Gnomad OTH AF: 0.0450

GnomAD2 exomes AF: 0.0463 AC: 11500 AN: 248498 AF XY: 0.0468

Gnomad AFR exome AF: 0.0115

Gnomad AMR exome AF: 0.0270

Gnomad ASJ exome AF: 0.0681

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0430

Gnomad NFE exome AF: 0.0708

Gnomad OTH exome AF: 0.0534

GnomAD4 exome AF: 0.0600 AC: 87483 AN: 1458592 Hom.: 3021 Cov.: 34 AF XY: 0.0588 AC XY: 42651 AN XY: 725708

African (AFR) AF: 0.00996 AC: 333 AN: 33432

American (AMR) AF: 0.0277 AC: 1239 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0668 AC: 1746 AN: 26134

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

South Asian (SAS) AF: 0.0180 AC: 1550 AN: 86184

European-Finnish (FIN) AF: 0.0438 AC: 2262 AN: 51702

Middle Eastern (MID) AF: 0.0509 AC: 238 AN: 4678

European-Non Finnish (NFE) AF: 0.0691 AC: 76793 AN: 1111818

Other (OTH) AF: 0.0551 AC: 3319 AN: 60228

GnomAD4 genome AF: 0.0449 AC: 6829 AN: 152218 Hom.: 228 Cov.: 32 AF XY: 0.0436 AC XY: 3245 AN XY: 74418

African (AFR) AF: 0.0122 AC: 505 AN: 41532

American (AMR) AF: 0.0403 AC: 616 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

South Asian (SAS) AF: 0.0185 AC: 89 AN: 4820

European-Finnish (FIN) AF: 0.0397 AC: 422 AN: 10618

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0711 AC: 4835 AN: 68012

Other (OTH) AF: 0.0440 AC: 93 AN: 2112

Alfa AF: 0.0594 Hom.: 144

Bravo AF: 0.0439

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: 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	-0.87
CADD	Benign	1.3
DANN	Benign	0.53
PhyloP100		-0.52
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: rs35410697; hg19: chr9-136289423; COSMIC: COSV63020647;