Genetic Variant ADAMTS7:p.Ser214Thr (chr15-78796769-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014272.5(ADAMTS7):c.640T>A(p.Ser214Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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. S214P) has been classified as Benign.

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

Not reported in ClinVar

Conservation

PhyloP100: -2.04

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0276362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ADAMTS7	NM_014272.5 link	c.640T>A	p.Ser214Thr	missense_variant	Exon 4 of 24	ENST00000388820.5	NP_055087.2
ADAMTS7	XM_047432122.1 link	c.640T>A	p.Ser214Thr	missense_variant	Exon 4 of 24		XP_047288078.1
ADAMTS7	XM_047432123.1 link	c.-120T>A		5_prime_UTR_variant	Exon 3 of 23		XP_047288079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ADAMTS7	ENST00000388820.5 link	c.640T>A	p.Ser214Thr	missense_variant	Exon 4 of 24	1	NM_014272.5	ENSP00000373472.4
ADAMTS7	ENST00000565793.5 link	n.537T>A		non_coding_transcript_exon_variant	Exon 3 of 12	2
ADAMTS7	ENST00000566303.5 link	n.703T>A		non_coding_transcript_exon_variant	Exon 4 of 10	5
ADAMTS7	ENST00000568712.1 link	n.652T>A		non_coding_transcript_exon_variant	Exon 4 of 15	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1457588

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725240

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111318

Other (OTH)

AF:

0.00

AC:

AN:

60328

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.12

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.010

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.055

M_CAP

Benign

0.011

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-2.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.12

REVEL

Benign

0.015

Sift

Benign

0.51

Sift4G

Benign

0.46

Polyphen

0.23

Vest4

0.076

MutPred

0.11

Loss of phosphorylation at S214 (P = 0.081);

MVP

0.27

MPC

0.18

ClinPred

0.077

GERP RS

-9.0

Varity_R

0.034

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over