rs3124768

Positions:

• chr9-133439376-G-A
• chr9-133439376-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_139027.6(ADAMTS13):​c.1716G>A​(p.Thr572=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,611,636 control chromosomes in the GnomAD database, including 255,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (25101 hom., cov: 33)
  • Exomes 𝑓: 0.56 (230424 hom.)
• Consequence: ADAMTS13 NM_139027.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.99

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 9-133439376-G-A is Benign according to our data. Variant chr9-133439376-G-A is described in ClinVar as [Benign]. Clinvar id is 769359.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.99 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS13	NM_139027.6	c.1716G>A	p.Thr572=	synonymous_variant	15/29	ENST00000355699.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS13	ENST00000355699.7	c.1716G>A	p.Thr572=	synonymous_variant	15/29	1	NM_139027.6	A2

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85905 AN: 152060 Hom.: 25067 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.525

GnomAD4 exome AF: 0.556 AC: 810938 AN: 1459458 Hom.: 230424 Cov.: 39 AF XY: 0.553 AC XY: 401801 AN XY: 726282

Gnomad4 AFR exome AF: 0.642

Gnomad4 AMR exome AF: 0.503

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.490

Gnomad4 FIN exome AF: 0.642

Gnomad4 NFE exome AF: 0.575

Gnomad4 OTH exome AF: 0.532

GnomAD4 genome AF: 0.565 AC: 85982 AN: 152178 Hom.: 25101 Cov.: 33 AF XY: 0.564 AC XY: 41978 AN XY: 74390

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.520

Alfa AF: 0.555 Hom.: 32152

Bravo AF: 0.553

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.037

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3124768; hg19: chr9-136304497;