rs4476282

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_030957.4(ADAMTS10):c.2283T>C(p.Pro761=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,613,782 control chromosomes in the GnomAD database, including 37,409 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. P761P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.22 ( 3738 hom., cov: 32)

Exomes 𝑓: 0.21 ( 33671 hom. )

Consequence

ADAMTS10
NM_030957.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.86

Variant links:

Genes affected

ADAMTS10 (HGNC:13201): (ADAM metallopeptidase with thrombospondin type 1 motif 10) This gene belongs to the ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin type-1 motifs) family of zinc-dependent proteases. ADAMTS proteases are complex secreted enzymes containing a prometalloprotease domain of the reprolysin type attached to an ancillary domain with a highly conserved structure that includes at least one thrombospondin type 1 repeat. They have been demonstrated to have important roles in connective tissue organization, coagulation, inflammation, arthritis, angiogenesis and cell migration. The product of this gene plays a major role in growth and in skin, lens, and heart development. It is also a candidate gene for autosomal recessive Weill-Marchesani syndrome. [provided by RefSeq, Jul 2008]

ADAMTS10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 19-8586678-A-G is Benign according to our data. Variant chr19-8586678-A-G is described in ClinVar as [Benign]. Clinvar id is 330587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-8586678-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.86 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS10	NM_030957.4 linkuse as main transcript	c.2283T>C	p.Pro761=	synonymous_variant	20/26	ENST00000597188.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS10	ENST00000597188.6 linkuse as main transcript	c.2283T>C	p.Pro761=	synonymous_variant	20/26	5	NM_030957.4	P1

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33350

AN:

151868

Hom.:

3740

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.217

GnomAD3 exomes

AF:

0.213

AC:

53351

AN:

250704

Hom.:

6042

AF XY:

0.207

AC XY:

28055

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.243

Gnomad ASJ exome

AF:

0.213

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.132

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.223

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.212

AC:

310219

AN:

1461794

Hom.:

33671

Cov.:

AF XY:

0.210

AC XY:

152699

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.229

Gnomad4 AMR exome

AF:

0.238

Gnomad4 ASJ exome

AF:

0.209

Gnomad4 EAS exome

AF:

0.135

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.302

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.202

GnomAD4 genome

AF:

0.220

AC:

33369

AN:

151988

Hom.:

3738

Cov.:

AF XY:

0.220

AC XY:

16356

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.223

Gnomad4 AMR

AF:

0.206

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.117

Gnomad4 SAS

AF:

0.144

Gnomad4 FIN

AF:

0.319

Gnomad4 NFE

AF:

0.221

Gnomad4 OTH

AF:

0.220

Alfa

AF:

0.214

Hom.:

3821

Bravo

AF:

0.211

Asia WGS

AF:

0.173

AC:

602

AN:

3478

EpiCase

AF:

0.220

EpiControl

AF:

0.221

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Weill-Marchesani syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

Cadd

Benign

0.077

Dann

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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