dbSNP rs370398327: ADAM7:p.Gly4Arg (chr8-24441118-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003817.4(ADAM7):c.10G>A(p.Gly4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000682 in 1,613,642 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000034 ( 1 hom. )

Consequence

ADAM7
NM_003817.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.105

Variant links:

Genes affected

ADAM7 (HGNC:214): (ADAM metallopeptidase domain 7) This gene encodes a member of the ADAMs family of zinc proteases. These transmembrane proteins play roles in multiple processes including cell signaling, adhesion and migration. The encoded protein lacks protease activity and may play roles in protein-protein interactions and cell adhesion processes including sperm-egg fusion. Mutations in this gene may be involved in the progression of melanoma. [provided by RefSeq, Oct 2011]

ADAM7 links:

ADAM7-AS1 (HGNC:56152): (ADAM7, ADAMDEC1 and ADAM28 antisense RNA 1)

ADAM7-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01895243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM7	NM_003817.4 link	c.10G>A	p.Gly4Arg	missense_variant	Exon 1 of 22	ENST00000175238.10	NP_003808.2	Q9H2U9-1A0A384MTL6
ADAM7-AS1	NR_125808.1 link	n.80-53127C>T		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM7	ENST00000175238.10 link	c.10G>A	p.Gly4Arg	missense_variant	Exon 1 of 22	1	NM_003817.4	ENSP00000175238.5		Q9H2U9-1

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251300

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1461390

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000394

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.0000954

Hom.:

Bravo

AF:

0.000499

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.2

DANN

Benign

0.89

DEOGEN2

Benign

0.0015

.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.54

T;T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.019

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.60

N;N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.093

Sift

Uncertain

0.015

D;T;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.027

.;B;.

Vest4

0.10

MutPred

0.73

Gain of methylation at G4 (P = 0.0222);Gain of methylation at G4 (P = 0.0222);Gain of methylation at G4 (P = 0.0222);

MVP

0.37

MPC

0.054

ClinPred

0.0078

GERP RS

-2.3

Varity_R

0.058

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over