Variant 15-78764060-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014272.5(ADAMTS7):c.4459G>A(p.Val1487Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000652 in 1,379,666 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

ADAMTS7
NM_014272.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.41

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADAMTS7	NM_014272.5 linkuse as main transcript	c.4459G>A	p.Val1487Met	missense_variant	21/24	ENST00000388820.5
ADAMTS7	XM_047432122.1 linkuse as main transcript	c.4459G>A	p.Val1487Met	missense_variant	21/24
ADAMTS7	XM_047432123.1 linkuse as main transcript	c.3700G>A	p.Val1234Met	missense_variant	20/23
ADAMTS7	XM_011521166.3 linkuse as main transcript	c.2713G>A	p.Val905Met	missense_variant	10/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS7	ENST00000388820.5 linkuse as main transcript	c.4459G>A	p.Val1487Met	missense_variant	21/24	1	NM_014272.5	P1
ADAMTS7	ENST00000569934.1 linkuse as main transcript	n.599G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000138

AC:

AN:

145200

Hom.:

AF XY:

0.0000130

AC XY:

AN XY:

77136

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000910

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000652

AC:

AN:

1379666

Hom.:

Cov.:

AF XY:

0.00000885

AC XY:

AN XY:

677882

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000281

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000655

Gnomad4 OTH exome

AF:

0.0000176

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000509

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

Sep 01, 2021

The c.4459G>A (p.V1487M) 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 4459, causing the valine (V) at amino acid position 1487 to be replaced by a methionine (M). 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

0.22

BayesDel_addAF

Benign

0.0070

BayesDel_noAF

Benign

-0.23

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Pathogenic

0.75

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.60

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.61

MetaSVM

Uncertain

0.085

MutationAssessor

Pathogenic

3.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.23

Sift

Uncertain

0.018

Sift4G

Uncertain

0.021

Polyphen

1.0

Vest4

0.52

MutPred

0.33

Gain of catalytic residue at V1487 (P = 5e-04);

MVP

0.58

MPC

0.68

ClinPred

0.98

GERP RS

4.4

Varity_R

0.23

gMVP

0.42

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

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