rs61753674

Positions:

chr8-39026751-C-T

Variant summary

Our verdict is Benign. Variant got -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

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:

ADAM9 (HGNC:):

ADAM9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 259174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-39026751-C-T is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM9	NM_003816.3 linkuse as main transcript	c.1071C>T	p.His357His	synonymous_variant	11/22	ENST00000487273.7	NP_003807.1	Q13443-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM9	ENST00000487273.7 linkuse as main transcript	c.1071C>T	p.His357His	synonymous_variant	11/22	1	NM_003816.3	ENSP00000419446.2		Q13443-1

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

GnomAD3 exomes

AF:

0.00743

AC:

1869

AN:

251458

Hom.:

AF XY:

0.00727

AC XY:

988

AN XY:

135902

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 SAS exome

AF:

0.00101

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

Gnomad4 AFR exome

AF:

0.00197

Gnomad4 AMR exome

AF:

0.00237

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00117

Gnomad4 FIN exome

AF:

0.00376

Gnomad4 NFE exome

AF:

0.0164

Gnomad4 OTH exome

AF:

0.0117

GnomAD4 genome

AF:

0.00822

AC:

1252

AN:

152252

Hom.:

Cov.:

AF XY:

0.00764

AC XY:

569

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00282

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00368

Gnomad4 NFE

AF:

0.0147

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.00792

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0118

EpiControl

AF:

0.0120

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	ADAM9: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 13, 2021	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Cone-rod dystrophy 9

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

4.8

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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