Genetic Variant ADAMTS7:p.Cys1553Cys (chr15-78763780-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_014272.5(ADAMTS7):c.4659C>T(p.Cys1553Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,593,752 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0017 ( 16 hom. )

Consequence

ADAMTS7
NM_014272.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.40

Variant links:

Genes affected

ADAMTS7 (HGNC:223): (ADAM metallopeptidase with thrombospondin type 1 motif 7) The protein encoded by this gene is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family. Members of this family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme contains two C-terminal TS motifs and may regulate vascular smooth muscle cell (VSMC) migration. Mutations in this gene may be associated with susceptibility to coronary artery disease. [provided by RefSeq, Feb 2016]

ADAMTS7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 15-78763780-G-A is Benign according to our data. Variant chr15-78763780-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 774498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.39 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS7	NM_014272.5 link	c.4659C>T	p.Cys1553Cys	synonymous_variant	Exon 22 of 24	ENST00000388820.5	NP_055087.2	Q9UKP4Q9UFZ4
ADAMTS7	XM_047432122.1 link	c.4659C>T	p.Cys1553Cys	synonymous_variant	Exon 22 of 24		XP_047288078.1
ADAMTS7	XM_047432123.1 link	c.3900C>T	p.Cys1300Cys	synonymous_variant	Exon 21 of 23		XP_047288079.1
ADAMTS7	XM_011521166.3 link	c.2913C>T	p.Cys971Cys	synonymous_variant	Exon 11 of 13		XP_011519468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS7	ENST00000388820.5 link	c.4659C>T	p.Cys1553Cys	synonymous_variant	Exon 22 of 24	1	NM_014272.5	ENSP00000373472.4		Q9UKP4
ADAMTS7	ENST00000569934.1 link	n.*171C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

195

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00172

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00209

AC:

446

AN:

213560

Hom.:

AF XY:

0.00246

AC XY:

287

AN XY:

116850

show subpopulations

Gnomad AFR exome

AF:

0.0000783

Gnomad AMR exome

AF:

0.000349

Gnomad ASJ exome

AF:

0.00404

Gnomad EAS exome

AF:

0.0000608

Gnomad SAS exome

AF:

0.00729

Gnomad FIN exome

AF:

0.000188

Gnomad NFE exome

AF:

0.00192

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00167

AC:

2401

AN:

1441422

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

1364

AN XY:

715788

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000421

Gnomad4 ASJ exome

AF:

0.00420

Gnomad4 EAS exome

AF:

0.0000766

Gnomad4 SAS exome

AF:

0.00749

Gnomad4 FIN exome

AF:

0.000457

Gnomad4 NFE exome

AF:

0.00131

Gnomad4 OTH exome

AF:

0.00234

GnomAD4 genome

AF:

0.00128

AC:

195

AN:

152330

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00848

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00172

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00202

Hom.:

Bravo

AF:

0.00102

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ADAMTS7: BP4, BP7, BS2 -

Aug 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.9

DANN

Benign

0.56

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