rs3743060

Variant names:

• chr15-78788284-G-A
• rs3743060
• NM_014272.5:c.1269C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate 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
• Publications: 4 publications found

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]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014272.5. 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
	ADAMTS7	NM_014272.5	MANE Select	c.1269C>T	p.Ala423Ala	synonymous	Exon 8 of 24	NP_055087.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS7	ENST00000388820.5	TSL:1 MANE Select	c.1269C>T	p.Ala423Ala	synonymous	Exon 8 of 24	ENSP00000373472.4	Q9UKP4
	ADAMTS7	ENST00000917170.1		c.1193C>T	p.Pro398Leu	missense	Exon 8 of 16	ENSP00000587229.1
	ADAMTS7	ENST00000972106.1		c.1269C>T	p.Ala423Ala	synonymous	Exon 8 of 24	ENSP00000642165.1

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

GnomAD2 exomes AF: 0.00145 AC: 365 AN: 251386 AF XY: 0.00130

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

African (AFR) AF: 0.000120 AC: 4 AN: 33468

American (AMR) AF: 0.00461 AC: 206 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00184 AC: 48 AN: 26134

East Asian (EAS) AF: 0.0102 AC: 403 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86242

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.000916 AC: 5 AN: 5458

European-Non Finnish (NFE) AF: 0.00114 AC: 1263 AN: 1111994

Other (OTH) AF: 0.00136 AC: 82 AN: 60362

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

African (AFR) AF: 0.000192 AC: 8 AN: 41580

American (AMR) AF: 0.00359 AC: 55 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00101 AC: 69 AN: 68018

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.000863 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.8
DANN	Benign	0.93
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs3743060; hg19: chr15-79080626;