8-39026823-G-GTTCTTTCT

Variant names:

• chr8-39026823-G-GTTCTTTCT
• rs10651669
• NM_003816.3:c.1130+18_1130+19insTCTTTCTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000487273.7(ADAM9):​c.1130+18_1130+19insTCTTTCTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: ADAM9 ENST00000487273.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.767
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000487273.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM9	NM_003816.3	MANE Select	c.1130+18_1130+19insTCTTTCTT		intron	N/A	NP_003807.1
	ADAM9	NR_027638.2		n.1221+18_1221+19insTCTTTCTT		intron	N/A
	ADAM9	NR_027639.2		n.1221+18_1221+19insTCTTTCTT		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM9	ENST00000487273.7	TSL:1 MANE Select	c.1130+18_1130+19insTCTTTCTT		intron	N/A	ENSP00000419446.2
	ADAM9	ENST00000379917.7	TSL:1	n.1130+18_1130+19insTCTTTCTT		intron	N/A	ENSP00000369249.3
	ADAM9	ENST00000468065.5	TSL:1	n.1130+18_1130+19insTCTTTCTT		intron	N/A	ENSP00000418737.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10651669; hg19: chr8-38884342;