rs147563206

Positions:

• chr9-133425555-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_139027.6(ADAMTS13):​c.357C>T​(p.Ser119Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,613,516 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (19 hom.)
• Consequence: ADAMTS13 NM_139027.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.173

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 9-133425555-C-T is Benign according to our data. Variant chr9-133425555-C-T is described in ClinVar as [Benign]. Clinvar id is 262447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.173 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00688 (1047/152222) while in subpopulation AFR AF= 0.0209 (868/41536). AF 95% confidence interval is 0.0197. There are 12 homozygotes in gnomad4. There are 486 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS13	NM_139027.6	c.357C>T	p.Ser119Ser	synonymous_variant	4/29	ENST00000355699.7	NP_620596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7	c.357C>T	p.Ser119Ser	synonymous_variant	4/29	1	NM_139027.6	ENSP00000347927.2

Frequencies

GnomAD3 genomes AF: 0.00688 AC: 1046 AN: 152104 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.00861

GnomAD3 exomes AF: 0.00316 AC: 789 AN: 249758 Hom.: 4 AF XY: 0.00259 AC XY: 350 AN XY: 135374

Gnomad AFR exome AF: 0.0237

Gnomad AMR exome AF: 0.00591

Gnomad ASJ exome AF: 0.00369

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.00312

GnomAD4 exome AF: 0.00167 AC: 2444 AN: 1461294 Hom.: 19 Cov.: 32 AF XY: 0.00158 AC XY: 1152 AN XY: 726932

Gnomad4 AFR exome AF: 0.0236

Gnomad4 AMR exome AF: 0.00582

Gnomad4 ASJ exome AF: 0.00253

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000952

Gnomad4 OTH exome AF: 0.00296

GnomAD4 genome AF: 0.00688 AC: 1047 AN: 152222 Hom.: 12 Cov.: 32 AF XY: 0.00653 AC XY: 486 AN XY: 74414

Gnomad4 AFR AF: 0.0209

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000882

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00427 Hom.: 3

Bravo AF: 0.00819

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00191

EpiControl AF: 0.00219

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 19, 2019	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Upshaw-Schulman syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	10
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs147563206; hg19: chr9-136290675;