rs4476282

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_030957.4(ADAMTS10):c.2283T>C(p.Pro761Pro) 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:6

Conservation

PhyloP100: -2.86

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

Weill-Marchesani syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Weill-Marchesani syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ADAMTS10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 330587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030957.4. 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
	ADAMTS10	NM_030957.4	MANE Select	c.2283T>C	p.Pro761Pro	synonymous	Exon 20 of 26	NP_112219.3	A0A0A0MQW6
	ADAMTS10	NM_001282352.2		c.744T>C	p.Pro248Pro	synonymous	Exon 7 of 13	NP_001269281.1	Q9H324-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAMTS10	ENST00000597188.6	TSL:5 MANE Select	c.2283T>C	p.Pro761Pro	synonymous	Exon 20 of 26	ENSP00000471851.1	A0A0A0MQW6
ADAMTS10	ENST00000270328.8	TSL:5	c.2283T>C	p.Pro761Pro	synonymous	Exon 19 of 25	ENSP00000270328.4	A0A0A0MQW6
ADAMTS10	ENST00000906412.1		c.2283T>C	p.Pro761Pro	synonymous	Exon 19 of 25	ENSP00000576471.1

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

GnomAD2 exomes

AF:

0.213

AC:

53351

AN:

250704

AF XY:

0.207

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 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

African (AFR)

AF:

0.229

AC:

7678

AN:

33480

American (AMR)

AF:

0.238

AC:

10623

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

5475

AN:

26134

East Asian (EAS)

AF:

0.135

AC:

5358

AN:

39700

South Asian (SAS)

AF:

0.130

AC:

11250

AN:

86258

European-Finnish (FIN)

AF:

0.302

AC:

16106

AN:

53336

Middle Eastern (MID)

AF:

0.225

AC:

1298

AN:

5768

European-Non Finnish (NFE)

AF:

0.216

AC:

240241

AN:

1112002

Other (OTH)

AF:

0.202

AC:

12190

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

16560

33120

49681

66241

82801

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8134

16268

24402

32536

40670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.220

AC:

33369

AN:

151988

Hom.:

3738

Cov.:

AF XY:

0.220

AC XY:

16356

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.223

AC:

9231

AN:

41454

American (AMR)

AF:

0.206

AC:

3139

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

671

AN:

3468

East Asian (EAS)

AF:

0.117

AC:

604

AN:

5168

South Asian (SAS)

AF:

0.144

AC:

693

AN:

4818

European-Finnish (FIN)

AF:

0.319

AC:

3371

AN:

10564

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

15021

AN:

67938

Other (OTH)

AF:

0.220

AC:

465

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1336

2673

4009

5346

6682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

336

672

1008

1344

1680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.217

Hom.:

6474

Bravo

AF:

0.211

Asia WGS

AF:

0.173

AC:

602

AN:

3478

EpiCase

AF:

0.220

EpiControl

AF:

0.221

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Weill-Marchesani syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.077

(source)

DANN

Benign

0.50

PhyloP100

-2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over