rs3118667

Positions:

• chr9-133425943-T-C

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.420T>C​(p.Ala140=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,613,002 control chromosomes in the GnomAD database, including 182,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (17440 hom., cov: 32)
  • Exomes 𝑓: 0.47 (165460 hom.)
• Consequence: ADAMTS13 NM_139027.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.339

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=-0.82).
• BP6: Variant 9-133425943-T-C is Benign according to our data. Variant chr9-133425943-T-C is described in ClinVar as [Benign]. Clinvar id is 769358.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.339 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS13	NM_139027.6	c.420T>C	p.Ala140=	synonymous_variant	5/29	ENST00000355699.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS13	ENST00000355699.7	c.420T>C	p.Ala140=	synonymous_variant	5/29	1	NM_139027.6	A2

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71558 AN: 151850 Hom.: 17411 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.433

GnomAD4 exome AF: 0.471 AC: 687479 AN: 1461034 Hom.: 165460 Cov.: 82 AF XY: 0.471 AC XY: 341951 AN XY: 726778

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.432

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.461

Gnomad4 FIN exome AF: 0.577

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.448

GnomAD4 genome AF: 0.471 AC: 71634 AN: 151968 Hom.: 17440 Cov.: 32 AF XY: 0.472 AC XY: 35045 AN XY: 74278

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.430

Alfa AF: 0.462 Hom.: 17122

Bravo AF: 0.457

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

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3118667; hg19: chr9-136291063;