Variant 15-78759425-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014272.5(ADAMTS7):c.5057G>A(p.Arg1686His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,591,890 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

ADAMTS7
NM_014272.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42

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=0.2968653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS7	NM_014272.5 linkuse as main transcript	c.5057G>A	p.Arg1686His	missense_variant	24/24	ENST00000388820.5	NP_055087.2	Q9UKP4Q9UFZ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS7	ENST00000388820.5 linkuse as main transcript	c.5057G>A	p.Arg1686His	missense_variant	24/24	1	NM_014272.5	ENSP00000373472.4		Q9UKP4

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000556

AC:

AN:

1439592

Hom.:

Cov.:

AF XY:

0.0000531

AC XY:

AN XY:

715626

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000203

Gnomad4 SAS exome

AF:

0.000141

Gnomad4 FIN exome

AF:

0.0000480

Gnomad4 NFE exome

AF:

0.0000379

Gnomad4 OTH exome

AF:

0.0000839

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.000185

AC:

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

Aug 13, 2021

The c.5057G>A (p.R1686H) alteration is located in exon 24 (coding exon 24) of the ADAMTS7 gene. This alteration results from a G to A substitution at nucleotide position 5057, causing the arginine (R) at amino acid position 1686 to be replaced by a histidine (H). 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

0.20

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

Eigen

Benign

0.026

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.73

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.11

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.32

MVP

0.46

MPC

0.76

ClinPred

0.12

GERP RS

2.0

Varity_R

0.095

gMVP

0.45

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