8-39026823-G-GTTCT

Variant names:

• chr8-39026823-G-GTTCT
• rs10651669
• NM_003816.3:c.1130+15_1130+18dupTCTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003816.3(ADAM9):​c.1130+15_1130+18dupTCTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 1,612,992 control chromosomes in the GnomAD database, including 503,834 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (49702 hom., cov: 0)
  • Exomes 𝑓: 0.79 (454132 hom.)
• Consequence: ADAM9 NM_003816.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.767
• Publications: 4 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 8-39026823-G-GTTCT is Benign according to our data. Variant chr8-39026823-G-GTTCT is described in ClinVar as Benign. ClinVar VariationId is 259175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM9	NM_003816.3	MANE Select	c.1130+15_1130+18dupTCTT		intron	N/A	NP_003807.1
	ADAM9	NR_027638.2		n.1221+15_1221+18dupTCTT		intron	N/A
	ADAM9	NR_027639.2		n.1221+15_1221+18dupTCTT		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+15_1130+18dupTCTT		intron	N/A	ENSP00000419446.2
	ADAM9	ENST00000379917.7	TSL:1	n.1130+15_1130+18dupTCTT		intron	N/A	ENSP00000369249.3
	ADAM9	ENST00000468065.5	TSL:1	n.1130+15_1130+18dupTCTT		intron	N/A	ENSP00000418737.1

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122485 AN: 151552 Hom.: 49645 Cov.: 0

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.798

GnomAD4 exome AF: 0.787 AC: 1149933 AN: 1461322 Hom.: 454132 Cov.: 38 AF XY: 0.783 AC XY: 568878 AN XY: 726982

African (AFR) AF: 0.838 AC: 28064 AN: 33476

American (AMR) AF: 0.891 AC: 39823 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 20122 AN: 26126

East Asian (EAS) AF: 0.943 AC: 37423 AN: 39678

South Asian (SAS) AF: 0.696 AC: 60002 AN: 86248

European-Finnish (FIN) AF: 0.807 AC: 43015 AN: 53316

Middle Eastern (MID) AF: 0.765 AC: 4411 AN: 5764

European-Non Finnish (NFE) AF: 0.782 AC: 869257 AN: 1111632

Other (OTH) AF: 0.792 AC: 47816 AN: 60368

GnomAD4 genome AF: 0.808 AC: 122607 AN: 151670 Hom.: 49702 Cov.: 0 AF XY: 0.810 AC XY: 60063 AN XY: 74108

African (AFR) AF: 0.840 AC: 34734 AN: 41330

American (AMR) AF: 0.852 AC: 12994 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2646 AN: 3464

East Asian (EAS) AF: 0.944 AC: 4860 AN: 5146

South Asian (SAS) AF: 0.716 AC: 3446 AN: 4814

European-Finnish (FIN) AF: 0.818 AC: 8578 AN: 10490

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52576 AN: 67862

Other (OTH) AF: 0.800 AC: 1681 AN: 2100

Alfa AF: 0.778 Hom.: 9588

Asia WGS AF: 0.821 AC: 2855 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Cone-rod dystrophy 9 (1)
-	-	1	Cone-Rod Dystrophy, Recessive (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

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;