rs34934621

chr9-133454478-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_139027.6(ADAMTS13):c.3108G>A(p.Ser1036=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 1,613,288 control chromosomes in the GnomAD database, including 1,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (106 hom., cov: 33)
  • Exomes 𝑓: 0.045 (1681 hom.)
• Consequence: ADAMTS13 NM_139027.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.43

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 9-133454478-G-A is Benign according to our data. Variant chr9-133454478-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133454478-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.43 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS13	NM_139027.6	c.3108G>A	p.Ser1036=	synonymous_variant	24/29	ENST00000355699.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS13	ENST00000355699.7	c.3108G>A	p.Ser1036=	synonymous_variant	24/29	1	NM_139027.6	A2

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4972 AN: 152212 Hom.: 107 Cov.: 33

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.0407

GnomAD3 exomes AF: 0.0327 AC: 8195 AN: 250278 Hom.: 201 AF XY: 0.0335 AC XY: 4549 AN XY: 135636

Gnomad AFR exome AF: 0.00925

Gnomad AMR exome AF: 0.0227

Gnomad ASJ exome AF: 0.0528

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0151

Gnomad FIN exome AF: 0.0177

Gnomad NFE exome AF: 0.0499

Gnomad OTH exome AF: 0.0408

GnomAD4 exome AF: 0.0449 AC: 65548 AN: 1460958 Hom.: 1681 Cov.: 32 AF XY: 0.0438 AC XY: 31866 AN XY: 726822

Gnomad4 AFR exome AF: 0.00824

Gnomad4 AMR exome AF: 0.0241

Gnomad4 ASJ exome AF: 0.0507

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0151

Gnomad4 FIN exome AF: 0.0170

Gnomad4 NFE exome AF: 0.0521

Gnomad4 OTH exome AF: 0.0412

GnomAD4 genome AF: 0.0326 AC: 4970 AN: 152330 Hom.: 106 Cov.: 33 AF XY: 0.0321 AC XY: 2393 AN XY: 74490

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.0373

Gnomad4 ASJ AF: 0.0527

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.0197

Gnomad4 NFE AF: 0.0499

Gnomad4 OTH AF: 0.0403

Alfa AF: 0.0425 Hom.: 96

Bravo AF: 0.0338

Asia WGS AF: 0.00895 AC: 31 AN: 3478

EpiCase AF: 0.0523

EpiControl AF: 0.0557

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

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	-0.78
Cadd	Benign	0.22
Dann	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs34934621; hg19: chr9-136319600;