15-78762547-C-T

Variant names:

• chr15-78762547-C-T
• rs139112621
• NM_014272.5:c.4759G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014272.5(ADAMTS7):​c.4759G>A​(p.Gly1587Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000314 in 1,554,134 control chromosomes in the GnomAD database, including 4 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1587R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00030 (4 hom.)
• Consequence: ADAMTS7 NM_014272.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.66
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010770023).
• BS2: High Homozygotes in GnomAdExome4 at 4 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.4759G>A	p.Gly1587Ser	missense	Exon 23 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.4759G>A	p.Gly1587Ser	missense	Exon 23 of 24	ENSP00000373472.4	Q9UKP4
	ADAMTS7	ENST00000972106.1		c.4732G>A	p.Gly1578Ser	missense	Exon 23 of 24	ENSP00000642165.1
	ADAMTS7	ENST00000972108.1		c.4666G>A	p.Gly1556Ser	missense	Exon 22 of 23	ENSP00000642167.1

Frequencies

GnomAD3 genomes AF: 0.000434 AC: 66 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0109

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000629 AC: 113 AN: 179788 AF XY: 0.000482

Gnomad AFR exome AF: 0.000232

Gnomad AMR exome AF: 0.0000406

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00811

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.000247

GnomAD4 exome AF: 0.000301 AC: 422 AN: 1401840 Hom.: 4 Cov.: 30 AF XY: 0.000291 AC XY: 202 AN XY: 695254

African (AFR) AF: 0.000195 AC: 6 AN: 30822

American (AMR) AF: 0.0000535 AC: 2 AN: 37376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22898

East Asian (EAS) AF: 0.00884 AC: 320 AN: 36188

South Asian (SAS) AF: 0.0000385 AC: 3 AN: 77952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5126

European-Non Finnish (NFE) AF: 0.0000314 AC: 34 AN: 1082940

Other (OTH) AF: 0.000987 AC: 57 AN: 57724

GnomAD4 genome AF: 0.000433 AC: 66 AN: 152294 Hom.: 0 Cov.: 33 AF XY: 0.000524 AC XY: 39 AN XY: 74448

African (AFR) AF: 0.000168 AC: 7 AN: 41582

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0109 AC: 56 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000854 Hom.: 1

Bravo AF: 0.000665

ExAC AF: 0.000829 AC: 100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.20
Sift	Benign	0.094	T
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.53
MVP		0.60
MPC		0.68
ClinPred		0.15	T
GERP RS		4.6
Varity_R		0.38
gMVP		0.49
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs139112621; hg19: chr15-79054889;