rs147563206

Variant names:

• chr9-133425555-C-T
• rs147563206
• NM_139027.6:c.357C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_139027.6(ADAMTS13):​c.357C>T​(p.Ser119Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,613,516 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (19 hom.)
• Consequence: ADAMTS13 NM_139027.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.173
• Publications: 3 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 9-133425555-C-T is Benign according to our data. Variant chr9-133425555-C-T is described in ClinVar as Benign. ClinVar VariationId is 262447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.173 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00688 (1047/152222) while in subpopulation AFR AF = 0.0209 (868/41536). AF 95% confidence interval is 0.0197. There are 12 homozygotes in GnomAd4. There are 486 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139027.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS13	NM_139027.6	MANE Select	c.357C>T	p.Ser119Ser	synonymous	Exon 4 of 29	NP_620596.2	Q76LX8-2
	ADAMTS13	NM_139025.5		c.357C>T	p.Ser119Ser	synonymous	Exon 4 of 29	NP_620594.1	Q76LX8-1
	ADAMTS13	NM_139026.6		c.357C>T	p.Ser119Ser	synonymous	Exon 4 of 29	NP_620595.1	Q76LX8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS13	ENST00000355699.7	TSL:1 MANE Select	c.357C>T	p.Ser119Ser	synonymous	Exon 4 of 29	ENSP00000347927.2	Q76LX8-2
	ADAMTS13	ENST00000371929.7	TSL:1	c.357C>T	p.Ser119Ser	synonymous	Exon 4 of 29	ENSP00000360997.3	Q76LX8-1
	ADAMTS13	ENST00000356589.6	TSL:1	c.357C>T	p.Ser119Ser	synonymous	Exon 4 of 29	ENSP00000348997.2	Q76LX8-3

Frequencies

GnomAD3 genomes AF: 0.00688 AC: 1046 AN: 152104 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.00861

GnomAD2 exomes AF: 0.00316 AC: 789 AN: 249758 AF XY: 0.00259

Gnomad AFR exome AF: 0.0237

Gnomad AMR exome AF: 0.00591

Gnomad ASJ exome AF: 0.00369

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.00312

GnomAD4 exome AF: 0.00167 AC: 2444 AN: 1461294 Hom.: 19 Cov.: 32 AF XY: 0.00158 AC XY: 1152 AN XY: 726932

African (AFR) AF: 0.0236 AC: 789 AN: 33476

American (AMR) AF: 0.00582 AC: 260 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00253 AC: 66 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52970

Middle Eastern (MID) AF: 0.0135 AC: 78 AN: 5764

European-Non Finnish (NFE) AF: 0.000952 AC: 1059 AN: 1111956

Other (OTH) AF: 0.00296 AC: 179 AN: 60384

GnomAD4 genome AF: 0.00688 AC: 1047 AN: 152222 Hom.: 12 Cov.: 32 AF XY: 0.00653 AC XY: 486 AN XY: 74414

African (AFR) AF: 0.0209 AC: 868 AN: 41536

American (AMR) AF: 0.00582 AC: 89 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68008

Other (OTH) AF: 0.00900 AC: 19 AN: 2112

Alfa AF: 0.00734 Hom.: 3

Bravo AF: 0.00819

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00191

EpiControl AF: 0.00219

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Upshaw-Schulman syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	10
DANN	Benign	0.64
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs147563206; hg19: chr9-136290675;