rs3124767

Variant names:

• chr9-133443421-T-C
• rs3124767
• NM_139027.6:c.2280T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-133443421-T-C
• chr9-133443421-T-G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_139027.6(ADAMTS13):​c.2280T>C​(p.Gly760Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 1,595,854 control chromosomes in the GnomAD database, including 267,720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (26927 hom., cov: 33)
  • Exomes 𝑓: 0.57 (240793 hom.)
• Consequence: ADAMTS13 NM_139027.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.49
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• congenital thrombotic thrombocytopenic purpura

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 9-133443421-T-C is Benign according to our data. Variant chr9-133443421-T-C is described in ClinVar as Benign. ClinVar VariationId is 769360.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS13	NM_139027.6	c.2280T>C	p.Gly760Gly	synonymous_variant	Exon 19 of 29	ENST00000355699.7	NP_620596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7	c.2280T>C	p.Gly760Gly	synonymous_variant	Exon 19 of 29	1	NM_139027.6	ENSP00000347927.2

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88886 AN: 151996 Hom.: 26882 Cov.: 33

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.571 AC: 824762 AN: 1443740 Hom.: 240793 Cov.: 77 AF XY: 0.569 AC XY: 408243 AN XY: 717788

African (AFR) AF: 0.677 AC: 22600 AN: 33366

American (AMR) AF: 0.487 AC: 21252 AN: 43640

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 10016 AN: 25866

East Asian (EAS) AF: 0.199 AC: 7831 AN: 39380

South Asian (SAS) AF: 0.504 AC: 42674 AN: 84664

European-Finnish (FIN) AF: 0.673 AC: 29148 AN: 43308

Middle Eastern (MID) AF: 0.478 AC: 2556 AN: 5342

European-Non Finnish (NFE) AF: 0.592 AC: 655950 AN: 1108334

Other (OTH) AF: 0.547 AC: 32735 AN: 59840

GnomAD4 genome AF: 0.585 AC: 88982 AN: 152114 Hom.: 26927 Cov.: 33 AF XY: 0.583 AC XY: 43385 AN XY: 74366

African (AFR) AF: 0.671 AC: 27878 AN: 41516

American (AMR) AF: 0.493 AC: 7534 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1340 AN: 3468

East Asian (EAS) AF: 0.202 AC: 1043 AN: 5156

South Asian (SAS) AF: 0.493 AC: 2376 AN: 4822

European-Finnish (FIN) AF: 0.664 AC: 7040 AN: 10610

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40114 AN: 67934

Other (OTH) AF: 0.528 AC: 1117 AN: 2114

Alfa AF: 0.576 Hom.: 7237

Bravo AF: 0.571

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.037
PhyloP100		-4.5

Splicing

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

Other links and lift over

dbSNP: rs3124767; hg19: chr9-136308542;