15-78764023-C-T

Variant summary

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

The NM_014272.5(ADAMTS7):c.4496G>A(p.Arg1499Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,541,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ADAMTS7
NM_014272.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.68

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:

Genome browser will be placed here

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=0.30254608).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADAMTS7	NM_014272.5 linkuse as main transcript	c.4496G>A	p.Arg1499Gln	missense_variant	21/24	ENST00000388820.5
ADAMTS7	XM_047432122.1 linkuse as main transcript	c.4496G>A	p.Arg1499Gln	missense_variant	21/24
ADAMTS7	XM_047432123.1 linkuse as main transcript	c.3737G>A	p.Arg1246Gln	missense_variant	20/23
ADAMTS7	XM_011521166.3 linkuse as main transcript	c.2750G>A	p.Arg917Gln	missense_variant	10/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS7	ENST00000388820.5 linkuse as main transcript	c.4496G>A	p.Arg1499Gln	missense_variant	21/24	1	NM_014272.5	P1
ADAMTS7	ENST00000569934.1 linkuse as main transcript	n.636G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000134

AC:

AN:

149186

Hom.:

AF XY:

0.0000126

AC XY:

AN XY:

79178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000175

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1388840

Hom.:

Cov.:

AF XY:

0.00000585

AC XY:

AN XY:

683754

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000333

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000559

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.4496G>A (p.R1499Q) alteration is located in exon 21 (coding exon 21) of the ADAMTS7 gene. This alteration results from a G to A substitution at nucleotide position 4496, causing the arginine (R) at amino acid position 1499 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.040

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.18

Sift

Uncertain

0.028

Sift4G

Uncertain

0.020

Polyphen

0.99

Vest4

0.30

MutPred

0.23

Loss of stability (P = 0.3289);

MVP

0.53

MPC

0.27

ClinPred

0.67

GERP RS

4.4

Varity_R

0.20

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over