chr9-133445796-C-T

Position:

chr9-133445796-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_139027.6(ADAMTS13):c.2708C>T(p.Ser903Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,590,318 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 41 hom. )

Consequence

ADAMTS13
NM_139027.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.625

Variant links:

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 links:

ADAMTS13 (HGNC:):

ADAMTS13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012989759).

BP6

Variant 9-133445796-C-T is Benign according to our data. Variant chr9-133445796-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 365555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133445796-C-T is described in Lovd as [Benign]. Variant chr9-133445796-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00156 (238/152232) while in subpopulation EAS AF= 0.0424 (219/5162). AF 95% confidence interval is 0.0378. There are 5 homozygotes in gnomad4. There are 145 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS13	NM_139027.6 linkuse as main transcript	c.2708C>T	p.Ser903Leu	missense_variant	21/29	ENST00000355699.7	NP_620596.2	Q76LX8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7 linkuse as main transcript	c.2708C>T	p.Ser903Leu	missense_variant	21/29	1	NM_139027.6	ENSP00000347927.2		Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

238

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0423

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00355

AC:

855

AN:

240894

Hom.:

AF XY:

0.00323

AC XY:

422

AN XY:

130732

show subpopulations

Gnomad AFR exome

AF:

0.0000625

Gnomad AMR exome

AF:

0.000118

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0449

Gnomad SAS exome

AF:

0.000886

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000934

Gnomad OTH exome

AF:

0.000509

GnomAD4 exome

AF:

0.00136

AC:

1956

AN:

1438086

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

946

AN XY:

710674

show subpopulations

Gnomad4 AFR exome

AF:

0.0000604

Gnomad4 AMR exome

AF:

0.0000912

Gnomad4 ASJ exome

AF:

0.0000393

Gnomad4 EAS exome

AF:

0.0445

Gnomad4 SAS exome

AF:

0.000930

Gnomad4 FIN exome

AF:

0.0000384

Gnomad4 NFE exome

AF:

0.0000265

Gnomad4 OTH exome

AF:

0.00164

GnomAD4 genome

AF:

0.00156

AC:

238

AN:

152232

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

145

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0424

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000204

Hom.:

Bravo

AF:

0.00177

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00339

AC:

411

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Upshaw-Schulman syndrome

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	May 25, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 16, 2016	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2023	ADAMTS13: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.2

DANN

Benign

0.96

DEOGEN2

Benign

0.13

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.27

T;T;T

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.92

N;N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.83

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.081

T;T;T

Sift4G

Benign

0.36

T;T;.

Polyphen

0.0

B;B;B

Vest4

0.62

MVP

0.55

MPC

0.30

ClinPred

0.0046

GERP RS

0.16

Varity_R

0.056

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over