Variant rs786205085 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_003816.3(ADAM9):c.1130+1G>A variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 66,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 32)

Consequence

ADAM9
NM_003816.3 splice_donor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.58

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:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 8-39026811-G-A is Pathogenic according to our data. Variant chr8-39026811-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 6876.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr8-39026811-G-A is described in Lovd as [Pathogenic]. Variant chr8-39026811-G-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM9	NM_003816.3 linkuse as main transcript	c.1130+1G>A		splice_donor_variant, intron_variant		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.1130+1G>A		splice_donor_variant, intron_variant		1	NM_003816.3	ENSP00000419446.2		Q13443-1

Frequencies

GnomAD3 genomes

AF:

0.0000151

AC:

AN:

66334

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000291

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000151

AC:

AN:

66334

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

31912

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000291

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Cone-rod dystrophy 9

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.32

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

1.2

Eigen_PC

Pathogenic

1.0

FATHMM_MKL

Uncertain

0.96

GERP RS

5.5

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.61

Position offset: 32

DS_DL_spliceai

0.99

Position offset: -1

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