dbSNP rs948628888: ADAMTS7:p.Glu1534Gln (chr15-78763839-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014272.5(ADAMTS7):c.4600G>C(p.Glu1534Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. E1534D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

ADAMTS7
NM_014272.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.46

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37585446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS7	NM_014272.5 link	c.4600G>C	p.Glu1534Gln	missense_variant	Exon 22 of 24	ENST00000388820.5	NP_055087.2	Q9UKP4Q9UFZ4
ADAMTS7	XM_047432122.1 link	c.4600G>C	p.Glu1534Gln	missense_variant	Exon 22 of 24		XP_047288078.1
ADAMTS7	XM_047432123.1 link	c.3841G>C	p.Glu1281Gln	missense_variant	Exon 21 of 23		XP_047288079.1
ADAMTS7	XM_011521166.3 link	c.2854G>C	p.Glu952Gln	missense_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.4600G>C	p.Glu1534Gln	missense_variant	Exon 22 of 24	1	NM_014272.5	ENSP00000373472.4		Q9UKP4
ADAMTS7	ENST00000569934.1 link	n.*112G>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1430338

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

709144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.09e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0073

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.81

M_CAP

Benign

0.074

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.080

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.7

REVEL

Benign

0.18

Sift

Benign

0.28

Sift4G

Benign

0.072

Polyphen

1.0

Vest4

0.36

MutPred

0.21

Gain of MoRF binding (P = 0.0835);

MVP

0.58

MPC

0.68

ClinPred

0.96

GERP RS

4.4

Varity_R

0.31

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over