Variant 8-24490869-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003817.4(ADAM7):c.1337A>G(p.Glu446Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,540 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ADAM7
NM_003817.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.05

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADAM7	NM_003817.4 linkuse as main transcript	c.1337A>G	p.Glu446Gly	missense_variant	13/22	ENST00000175238.10	NP_003808.2
ADAM7-AS1	NR_125808.1 linkuse as main transcript	n.79+57671T>C		intron_variant, non_coding_transcript_variant
ADAM7-AS2	NR_125809.1 linkuse as main transcript	n.748-363T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM7	ENST00000175238.10 linkuse as main transcript	c.1337A>G	p.Glu446Gly	missense_variant	13/22	1	NM_003817.4	ENSP00000175238	P2	Q9H2U9-1
ADAM7-AS2	ENST00000519364.5 linkuse as main transcript	n.708-363T>C		intron_variant, non_coding_transcript_variant		5
ADAM7-AS1	ENST00000519689.1 linkuse as main transcript	n.185-102878T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461540

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727056

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 10, 2021

The c.1337A>G (p.E446G) alteration is located in exon 13 (coding exon 13) of the ADAM7 gene. This alteration results from a A to G substitution at nucleotide position 1337, causing the glutamic acid (E) at amino acid position 446 to be replaced by a glycine (G). 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

0.13

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;T;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;.;.

MutationTaster

Benign

0.96

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-5.5

D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.040

D;D;T

Polyphen

1.0

D;.;D

Vest4

0.34

MutPred

0.50

Loss of glycosylation at T441 (P = 0.1656);Loss of glycosylation at T441 (P = 0.1656);.;

MVP

0.33

MPC

0.10

ClinPred

0.99

GERP RS

3.2

Varity_R

0.51

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