rs3118667

Variant names:

• chr9-133425943-T-C
• rs3118667
• NM_139027.6:c.420T>C

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.420T>C​(p.Ala140Ala) 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
• Publications: 53 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=-0.82).
• BP6: Variant 9-133425943-T-C is Benign according to our data. Variant chr9-133425943-T-C is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
ADAMTS13	NM_139027.6	c.420T>C	p.Ala140Ala	synonymous_variant	Exon 5 of 29	ENST00000355699.7	NP_620596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7	c.420T>C	p.Ala140Ala	synonymous_variant	Exon 5 of 29	1	NM_139027.6	ENSP00000347927.2

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

African (AFR) AF: 0.520 AC: 17404 AN: 33478

American (AMR) AF: 0.432 AC: 19283 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 7848 AN: 26136

East Asian (EAS) AF: 0.165 AC: 6565 AN: 39698

South Asian (SAS) AF: 0.461 AC: 39728 AN: 86254

European-Finnish (FIN) AF: 0.577 AC: 30473 AN: 52772

Middle Eastern (MID) AF: 0.378 AC: 2183 AN: 5768

European-Non Finnish (NFE) AF: 0.483 AC: 536925 AN: 1111870

Other (OTH) AF: 0.448 AC: 27070 AN: 60384

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

African (AFR) AF: 0.514 AC: 21274 AN: 41422

American (AMR) AF: 0.416 AC: 6349 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1022 AN: 3468

East Asian (EAS) AF: 0.171 AC: 884 AN: 5160

South Asian (SAS) AF: 0.449 AC: 2166 AN: 4822

European-Finnish (FIN) AF: 0.569 AC: 6010 AN: 10566

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32504 AN: 67938

Other (OTH) AF: 0.430 AC: 908 AN: 2114

Alfa AF: 0.468 Hom.: 48195

Bravo AF: 0.457

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	-0.82
CADD	Benign	1.6
PhyloP100		0.34

Splicing

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

Other links and lift over

dbSNP: rs3118667; hg19: chr9-136291063;