9-133422087-T-C

Position:

• chr9-133422087-T-C

Variant summary

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

The ENST00000371929(ADAMTS13):​c.-357T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 294,420 control chromosomes in the GnomAD database, including 914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.076 (500 hom., cov: 32)
  • Exomes 𝑓: 0.068 (414 hom.)
• Consequence: ADAMTS13 ENST00000371929 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.68

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 9-133422087-T-C is Benign according to our data. Variant chr9-133422087-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 365531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS13	XM_017014232.2	c.93+109T>C		intron_variant			XP_016869721.1
ADAMTS13	XM_017014233.2	c.-285-1014T>C		intron_variant			XP_016869722.1
ADAMTS13	NR_024514.3	n.309-1014T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000371929	c.-357T>C		5_prime_UTR_variant	1/29	1		ENSP00000360997.3
ADAMTS13	ENST00000485925.5	n.288-1014T>C		intron_variant		1
ADAMTS13	ENST00000371916	c.-1101T>C		5_prime_UTR_variant	1/26	5		ENSP00000360984.2

Frequencies

GnomAD3 genomes AF: 0.0759 AC: 11544 AN: 152052 Hom.: 500 Cov.: 32

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0752

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.0728

GnomAD4 exome AF: 0.0684 AC: 9724 AN: 142252 Hom.: 414 Cov.: 0 AF XY: 0.0641 AC XY: 4671 AN XY: 72870

Gnomad4 AFR exome AF: 0.0850

Gnomad4 AMR exome AF: 0.0516

Gnomad4 ASJ exome AF: 0.0695

Gnomad4 EAS exome AF: 0.000130

Gnomad4 SAS exome AF: 0.0217

Gnomad4 FIN exome AF: 0.0526

Gnomad4 NFE exome AF: 0.0822

Gnomad4 OTH exome AF: 0.0733

GnomAD4 genome AF: 0.0759 AC: 11556 AN: 152168 Hom.: 500 Cov.: 32 AF XY: 0.0740 AC XY: 5508 AN XY: 74400

Gnomad4 AFR AF: 0.0857

Gnomad4 AMR AF: 0.0582

Gnomad4 ASJ AF: 0.0752

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0204

Gnomad4 FIN AF: 0.0547

Gnomad4 NFE AF: 0.0878

Gnomad4 OTH AF: 0.0720

Alfa AF: 0.0877 Hom.: 105

Bravo AF: 0.0781

Asia WGS AF: 0.0200 AC: 68 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

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	-0.97
CADD	Benign	1.5
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs34265876; hg19: chr9-136287207;