dbSNP rs3743060: ADAMTS7:p.Ala423Ala (chr15-78788284-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2

The NM_014272.5(ADAMTS7):c.1269C>T(p.Ala423Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,613,810 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 12 hom. )

Consequence

ADAMTS7
NM_014272.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.680

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.081).

BP7

Synonymous conserved (PhyloP=-0.68 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS7	NM_014272.5 link	c.1269C>T	p.Ala423Ala	synonymous_variant	Exon 8 of 24	ENST00000388820.5	NP_055087.2	Q9UKP4Q9UFZ4
ADAMTS7	XM_047432122.1 link	c.1269C>T	p.Ala423Ala	synonymous_variant	Exon 8 of 24		XP_047288078.1
ADAMTS7	XM_047432123.1 link	c.510C>T	p.Ala170Ala	synonymous_variant	Exon 7 of 23		XP_047288079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADAMTS7	ENST00000388820.5 link	c.1269C>T	p.Ala423Ala	synonymous_variant	Exon 8 of 24	1	NM_014272.5	ENSP00000373472.4	Q9UKP4
ADAMTS7	ENST00000565793.5 link	n.1166C>T		non_coding_transcript_exon_variant	Exon 7 of 12	2
ADAMTS7	ENST00000566303.5 link	n.1256C>T		non_coding_transcript_exon_variant	Exon 8 of 10	5
ADAMTS7	ENST00000568712.1 link	n.1281C>T		non_coding_transcript_exon_variant	Exon 8 of 15	2

Frequencies

GnomAD3 genomes

AF:

0.00107

AC:

163

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00328

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00145

AC:

365

AN:

251386

AF XY:

0.00130

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00414

Gnomad ASJ exome

AF:

0.00218

Gnomad EAS exome

AF:

0.00348

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00106

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00138

AC:

2023

AN:

1461500

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

939

AN XY:

727042

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33468

American (AMR)

AF:

0.00461

AC:

206

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00184

AC:

AN:

26134

East Asian (EAS)

AF:

0.0102

AC:

403

AN:

39700

South Asian (SAS)

AF:

0.000116

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000916

AC:

AN:

5458

European-Non Finnish (NFE)

AF:

0.00114

AC:

1263

AN:

1111994

Other (OTH)

AF:

0.00136

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

122

244

367

489

611

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.00107

AC:

163

AN:

152310

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41580

American (AMR)

AF:

0.00359

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00328

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00101

AC:

AN:

68018

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000863

Hom.:

Bravo

AF:

0.00132

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.8

(source)

DANN

Benign

0.93

PhyloP100

-0.68

Mutation Taster

=100/0

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over