Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003816.3(ADAM9):c.1071C>T(p.His357His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,614,086 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 11 hom., cov: 32)

Exomes 𝑓: 0.013 ( 166 hom. )

Consequence

ADAM9
NM_003816.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.461

Publications

3 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 Gene-Disease associations (from GenCC):

ADAM9-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
cone-rod dystrophy 9
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ADAM9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 8-39026751-C-T is Benign according to our data. Variant chr8-39026751-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.461 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00822 (1252/152252) while in subpopulation NFE AF = 0.0147 (1001/68020). AF 95% confidence interval is 0.014. There are 11 homozygotes in GnomAd4. There are 569 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 11 AD,AR gene

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
ADAM9	NM_003816.3	MANE Select	c.1071C>T	p.His357His	synonymous	Exon 11 of 22	NP_003807.1
ADAM9	NR_027638.2		n.1162C>T		non_coding_transcript_exon	Exon 11 of 21
ADAM9	NR_027639.2		n.1162C>T		non_coding_transcript_exon	Exon 11 of 20

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADAM9	ENST00000487273.7	TSL:1 MANE Select	c.1071C>T	p.His357His	synonymous	Exon 11 of 22	ENSP00000419446.2
ADAM9	ENST00000379917.7	TSL:1	n.1071C>T		non_coding_transcript_exon	Exon 11 of 21	ENSP00000369249.3
ADAM9	ENST00000468065.5	TSL:1	n.1071C>T		non_coding_transcript_exon	Exon 11 of 20	ENSP00000418737.1

Frequencies

GnomAD3 genomes

AF:

0.00823

AC:

1252

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00282

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00368

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0147

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.00743

AC:

1869

AN:

251458

AF XY:

0.00727

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00351

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.00847

GnomAD4 exome

AF:

0.0133

AC:

19434

AN:

1461834

Hom.:

166

Cov.:

AF XY:

0.0128

AC XY:

9314

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00197

AC:

AN:

33480

American (AMR)

AF:

0.00237

AC:

106

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000536

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00117

AC:

101

AN:

86258

European-Finnish (FIN)

AF:

0.00376

AC:

201

AN:

53418

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0164

AC:

18234

AN:

1111976

Other (OTH)

AF:

0.0117

AC:

708

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1079

2158

3238

4317

5396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

722

1444

2166

2888

3610

<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:

0.00822

AC:

1252

AN:

152252

Hom.:

Cov.:

AF XY:

0.00764

AC XY:

569

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00282

AC:

117

AN:

41548

American (AMR)

AF:

0.00477

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00368

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0147

AC:

1001

AN:

68020

Other (OTH)

AF:

0.00711

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

123

185

246

308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0115

Hom.:

Bravo

AF:

0.00792

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0118

EpiControl

AF:

0.0120

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Cone-rod dystrophy 9 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

4.8

(source)

DANN

Benign

0.83

PhyloP100

-0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(source)

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

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

rs61753674

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over