rs3124768

Variant names:

• chr9-133439376-G-A
• rs3124768
• NM_139027.6:c.1716G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-133439376-G-A
• chr9-133439376-G-T

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.1716G>A​(p.Thr572Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,611,636 control chromosomes in the GnomAD database, including 255,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. T572T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.57 (25101 hom., cov: 33)
  • Exomes 𝑓: 0.56 (230424 hom.)
• Consequence: ADAMTS13 NM_139027.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.99
• Publications: 42 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=-1.0).
• BP6: Variant 9-133439376-G-A is Benign according to our data. Variant chr9-133439376-G-A is described in ClinVar as Benign. ClinVar VariationId is 769359.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.99 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

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.1716G>A	p.Thr572Thr	synonymous	Exon 15 of 29	NP_620596.2	Q76LX8-2
	ADAMTS13	NM_139025.5		c.1716G>A	p.Thr572Thr	synonymous	Exon 15 of 29	NP_620594.1	Q76LX8-1
	ADAMTS13	NM_139026.6		c.1623G>A	p.Thr541Thr	synonymous	Exon 15 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.1716G>A	p.Thr572Thr	synonymous	Exon 15 of 29	ENSP00000347927.2	Q76LX8-2
	ADAMTS13	ENST00000371929.7	TSL:1	c.1716G>A	p.Thr572Thr	synonymous	Exon 15 of 29	ENSP00000360997.3	Q76LX8-1
	ADAMTS13	ENST00000356589.6	TSL:1	c.1623G>A	p.Thr541Thr	synonymous	Exon 15 of 29	ENSP00000348997.2	Q76LX8-3

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85905 AN: 152060 Hom.: 25067 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.525

GnomAD4 exome AF: 0.556 AC: 810938 AN: 1459458 Hom.: 230424 Cov.: 39 AF XY: 0.553 AC XY: 401801 AN XY: 726282

African (AFR) AF: 0.642 AC: 21477 AN: 33442

American (AMR) AF: 0.503 AC: 22488 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 9730 AN: 26100

East Asian (EAS) AF: 0.191 AC: 7562 AN: 39666

South Asian (SAS) AF: 0.490 AC: 42228 AN: 86198

European-Finnish (FIN) AF: 0.642 AC: 34259 AN: 53384

Middle Eastern (MID) AF: 0.470 AC: 2708 AN: 5760

European-Non Finnish (NFE) AF: 0.575 AC: 638411 AN: 1109908

Other (OTH) AF: 0.532 AC: 32075 AN: 60284

GnomAD4 genome AF: 0.565 AC: 85982 AN: 152178 Hom.: 25101 Cov.: 33 AF XY: 0.564 AC XY: 41978 AN XY: 74390

African (AFR) AF: 0.639 AC: 26508 AN: 41510

American (AMR) AF: 0.503 AC: 7701 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3472

East Asian (EAS) AF: 0.192 AC: 997 AN: 5180

South Asian (SAS) AF: 0.479 AC: 2306 AN: 4816

European-Finnish (FIN) AF: 0.633 AC: 6696 AN: 10586

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38857 AN: 68000

Other (OTH) AF: 0.520 AC: 1098 AN: 2112

Alfa AF: 0.561 Hom.: 89888

Bravo AF: 0.553

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.037
PhyloP100		-6.0

Splicing

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

Other links and lift over

dbSNP: rs3124768; hg19: chr9-136304497;