9-133433609-C-G

Position:

• chr9-133433609-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139027.6(ADAMTS13):​c.1245-32C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,613,598 control chromosomes in the GnomAD database, including 254,935 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.56 (25075 hom., cov: 32)
  • Exomes 𝑓: 0.55 (229860 hom.)
• Consequence: ADAMTS13 NM_139027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS13	NM_139027.6	c.1245-32C>G		intron_variant		ENST00000355699.7	NP_620596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7	c.1245-32C>G		intron_variant		1	NM_139027.6	ENSP00000347927	A2

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85785 AN: 151890 Hom.: 25040 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.554 AC: 810345 AN: 1461590 Hom.: 229860 Cov.: 53 AF XY: 0.552 AC XY: 401183 AN XY: 727082

Gnomad4 AFR exome AF: 0.644

Gnomad4 AMR exome AF: 0.503

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.190

Gnomad4 SAS exome AF: 0.479

Gnomad4 FIN exome AF: 0.642

Gnomad4 NFE exome AF: 0.575

Gnomad4 OTH exome AF: 0.531

GnomAD4 genome AF: 0.565 AC: 85864 AN: 152008 Hom.: 25075 Cov.: 32 AF XY: 0.564 AC XY: 41926 AN XY: 74308

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.519

Alfa AF: 0.506 Hom.: 3190

Bravo AF: 0.553

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs739469; hg19: chr9-136298729;