Genetic Variant ADAMTS7:p.Ala23Asp (chr15-78811153-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014272.5(ADAMTS7):c.68C>A(p.Ala23Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ADAMTS7
NM_014272.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

Publications

0 publications found

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:

MORF4L1 (HGNC:16989): (mortality factor 4 like 1) Enables protein N-terminus binding activity. Involved in double-strand break repair via homologous recombination and histone modification. Located in nuclear speck. Part of NuA4 histone acetyltransferase complex and Sin3 complex. [provided by Alliance of Genome Resources, Apr 2022]

MORF4L1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.68C>A	p.Ala23Asp	missense	Exon 1 of 24	NP_055087.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAMTS7	ENST00000388820.5	TSL:1 MANE Select	c.68C>A	p.Ala23Asp	missense	Exon 1 of 24	ENSP00000373472.4	Q9UKP4
ADAMTS7	ENST00000972106.1		c.68C>A	p.Ala23Asp	missense	Exon 1 of 24	ENSP00000642165.1
ADAMTS7	ENST00000972107.1		c.68C>A	p.Ala23Asp	missense	Exon 1 of 24	ENSP00000642166.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1078048

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

509022

African (AFR)

AF:

0.00

AC:

AN:

22898

American (AMR)

AF:

0.00

AC:

AN:

8366

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14328

East Asian (EAS)

AF:

0.00

AC:

AN:

26460

South Asian (SAS)

AF:

0.00

AC:

AN:

19478

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2912

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

918910

Other (OTH)

AF:

0.00

AC:

AN:

43588

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.0088

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.011

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.67

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

PhyloP100

1.1

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.3

REVEL

Benign

0.25

Sift

Uncertain

0.015

Sift4G

Benign

0.12

Polyphen

0.99

Vest4

0.55

MutPred

0.60

Gain of relative solvent accessibility (P = 0.0479)

MVP

0.73

MPC

0.28

ClinPred

0.28

GERP RS

1.2

PromoterAI

0.097

Neutral

(source)

Varity_R

0.38

gMVP

0.50

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over