dbSNP rs148707472: ADAM9:p.Val26Val (chr8-38997141-C-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003816.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAM9	NM_003816.3	MANE Select	c.78C>A	p.Val26Val	synonymous	Exon 1 of 22	NP_003807.1	Q13443-1
ADAM9	NR_027638.2		n.169C>A		non_coding_transcript_exon	Exon 1 of 21
ADAM9	NR_027639.2		n.169C>A		non_coding_transcript_exon	Exon 1 of 20

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAM9	ENST00000487273.7	TSL:1 MANE Select	c.78C>A	p.Val26Val	synonymous	Exon 1 of 22	ENSP00000419446.2	Q13443-1
ADAM9	ENST00000379917.7	TSL:1	n.78C>A		non_coding_transcript_exon	Exon 1 of 21	ENSP00000369249.3	Q13443-2
ADAM9	ENST00000468065.5	TSL:1	n.78C>A		non_coding_transcript_exon	Exon 1 of 20	ENSP00000418737.1	F8WC54

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

GnomAD2 exomes

AF:

0.0404

AC:

9537

AN:

236188

AF XY:

0.0406

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 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

African (AFR)

AF:

0.00789

AC:

264

AN:

33444

American (AMR)

AF:

0.0354

AC:

1581

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.0493

AC:

1284

AN:

26064

East Asian (EAS)

AF:

0.000126

AC:

AN:

39656

South Asian (SAS)

AF:

0.0123

AC:

1059

AN:

86138

European-Finnish (FIN)

AF:

0.0798

AC:

3380

AN:

42368

Middle Eastern (MID)

AF:

0.0452

AC:

260

AN:

5748

European-Non Finnish (NFE)

AF:

0.0539

AC:

59852

AN:

1111230

Other (OTH)

AF:

0.0463

AC:

2788

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

3893

7785

11678

15570

19463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2142

4284

6426

8568

10710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0396

AC:

6028

AN:

152098

Hom.:

147

Cov.:

AF XY:

0.0391

AC XY:

2906

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0102

AC:

422

AN:

41518

American (AMR)

AF:

0.0494

AC:

755

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0548

AC:

190

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.0127

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0716

AC:

758

AN:

10588

Middle Eastern (MID)

AF:

0.0651

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0546

AC:

3708

AN:

67954

Other (OTH)

AF:

0.0421

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

287

574

861

1148

1435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0404

Hom.:

Bravo

AF:

0.0370

Asia WGS

AF:

0.00693

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Cone-rod dystrophy 9 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

0.11

PromoterAI

-0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over