Variant 8-24493099-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003817.4(ADAM7):c.1712G>C(p.Gly571Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ADAM7
NM_003817.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

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-AS2 (HGNC:56153): (ADAM7 antisense RNA 2)

ADAM7-AS2 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 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=0.33614996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM7	NM_003817.4 link	c.1712G>C	p.Gly571Ala	missense_variant	16/22	ENST00000175238.10	NP_003808.2	Q9H2U9-1A0A384MTL6
ADAM7-AS1	NR_125808.1 link	n.79+55441C>G		intron_variant
ADAM7-AS2	NR_125809.1 link	n.447-939C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM7	ENST00000175238.10 link	c.1712G>C	p.Gly571Ala	missense_variant	16/22	1	NM_003817.4	ENSP00000175238.5		Q9H2U9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459832

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726256

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 05, 2024

The c.1712G>C (p.G571A) alteration is located in exon 16 (coding exon 16) of the ADAM7 gene. This alteration results from a G to C substitution at nucleotide position 1712, causing the glycine (G) at amino acid position 571 to be replaced by an alanine (A). 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

0.17

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

T;T;.

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.8

M;.;.

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Benign

0.25

Sift

Benign

0.045

D;D;T

Sift4G

Benign

0.070

T;D;D

Polyphen

1.0

D;.;D

Vest4

0.16

MutPred

0.58

Loss of disorder (P = 0.0973);Loss of disorder (P = 0.0973);.;

MVP

0.45

MPC

0.31

ClinPred

0.98

GERP RS

4.8

Varity_R

0.21

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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