NM_003816.3:c.78C>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003816.3(ADAM9):c.78C>A(p.Val26Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 1,601,552 control chromosomes in the GnomAD database, including 2,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 147 hom., cov: 32)

Exomes 𝑓: 0.049 ( 1978 hom. )

Consequence

ADAM9
NM_003816.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.113

Variant links:

Genes affected

ADAM9 (HGNC:216): (ADAM metallopeptidase domain 9) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The protein encoded by this gene interacts with SH3 domain-containing proteins, binds mitotic arrest deficient 2 beta protein, and is also involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. Several alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jul 2010]

ADAM9 links:

TM2D2 (HGNC:24127): (TM2 domain containing 2) The protein encoded by this gene contains a structural module related to that of the seven transmembrane domain G protein-coupled receptor superfamily. This protein has sequence and structural similarities to the beta-amyloid binding protein (BBP), but, unlike BBP, it does not regulate a response to beta-amyloid peptide. This protein may have regulatory roles in cell death or proliferation signal cascades. This gene has multiple alternatively spliced transcript variants which encode two different isoforms. [provided by RefSeq, Jul 2008]

TM2D2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 8-38997141-C-A is Benign according to our data. Variant chr8-38997141-C-A is described in ClinVar as [Benign]. Clinvar id is 259176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.113 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM9	NM_003816.3 link	c.78C>A	p.Val26Val	synonymous_variant	Exon 1 of 22	ENST00000487273.7	NP_003807.1	Q13443-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM9	ENST00000487273.7 link	c.78C>A	p.Val26Val	synonymous_variant	Exon 1 of 22	1	NM_003816.3	ENSP00000419446.2		Q13443-1

Frequencies

GnomAD3 genomes

AF:

0.0396

AC:

6023

AN:

151982

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0102

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0494

Gnomad ASJ

AF:

0.0548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0716

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.0546

Gnomad OTH

AF:

0.0426

GnomAD3 exomes

AF:

0.0404

AC:

9537

AN:

236188

Hom.:

259

AF XY:

0.0406

AC XY:

5251

AN XY:

129266

show subpopulations

Gnomad AFR exome

AF:

0.00892

Gnomad AMR exome

AF:

0.0326

Gnomad ASJ exome

AF:

0.0532

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0124

Gnomad FIN exome

AF:

0.0782

Gnomad NFE exome

AF:

0.0555

Gnomad OTH exome

AF:

0.0522

GnomAD4 exome

AF:

0.0486

AC:

70473

AN:

1449454

Hom.:

1978

Cov.:

AF XY:

0.0479

AC XY:

34575

AN XY:

721516

show subpopulations

Gnomad4 AFR exome

AF:

0.00789

Gnomad4 AMR exome

AF:

0.0354

Gnomad4 ASJ exome

AF:

0.0493

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0123

Gnomad4 FIN exome

AF:

0.0798

Gnomad4 NFE exome

AF:

0.0539

Gnomad4 OTH exome

AF:

0.0463

GnomAD4 genome

AF:

0.0396

AC:

6028

AN:

152098

Hom.:

147

Cov.:

AF XY:

0.0391

AC XY:

2906

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0102

Gnomad4 AMR

AF:

0.0494

Gnomad4 ASJ

AF:

0.0548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0127

Gnomad4 FIN

AF:

0.0716

Gnomad4 NFE

AF:

0.0546

Gnomad4 OTH

AF:

0.0421

Alfa

AF:

0.0404

Hom.:

Bravo

AF:

0.0370

Asia WGS

AF:

0.00693

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:2

Oct 25, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cone-rod dystrophy 9

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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