rs3743060

Positions:

• chr15-78788284-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.680

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• 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/exons	MANE	Protein	UniProt
ADAMTS7	NM_014272.5	c.1269C>T	p.Ala423Ala	synonymous_variant	8/24	ENST00000388820.5	NP_055087.2
ADAMTS7	XM_047432122.1	c.1269C>T	p.Ala423Ala	synonymous_variant	8/24		XP_047288078.1
ADAMTS7	XM_047432123.1	c.510C>T	p.Ala170Ala	synonymous_variant	7/23		XP_047288079.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00107 AC: 163 AN: 152192 Hom.: 0 Cov.: 33

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

GnomAD3 exomes AF: 0.00145 AC: 365 AN: 251386 Hom.: 0 AF XY: 0.00130 AC XY: 177 AN XY: 135858

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 SAS exome AF: 0.0000980

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.: 12 Cov.: 31 AF XY: 0.00129 AC XY: 939 AN XY: 727042

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.00461

Gnomad4 ASJ exome AF: 0.00184

Gnomad4 EAS exome AF: 0.0102

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.00114

Gnomad4 OTH exome AF: 0.00136

GnomAD4 genome AF: 0.00107 AC: 163 AN: 152310 Hom.: 0 Cov.: 33 AF XY: 0.00111 AC XY: 83 AN XY: 74470

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.00359

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00101

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.00132

Asia WGS AF: 0.00231 AC: 8 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
DANN	Benign	0.93

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

Other links and lift over

dbSNP: rs3743060; hg19: chr15-79080626;