chr8-39026823-G-GTTCT

Position:

• chr8-39026823-G-GTTCT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003816.3(ADAM9):​c.1130+15_1130+18dup 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM9	NM_003816.3	c.1130+15_1130+18dup		intron_variant		ENST00000487273.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM9	ENST00000487273.7	c.1130+15_1130+18dup		intron_variant		1	NM_003816.3	P1

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

Gnomad4 AFR exome AF: 0.838

Gnomad4 AMR exome AF: 0.891

Gnomad4 ASJ exome AF: 0.770

Gnomad4 EAS exome AF: 0.943

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.807

Gnomad4 NFE exome AF: 0.782

Gnomad4 OTH exome AF: 0.792

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

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.800

Alfa AF: 0.778 Hom.: 9588

Asia WGS AF: 0.821 AC: 2855 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 28, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Cone-rod dystrophy 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Cone-Rod Dystrophy, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10651669; hg19: chr8-38884342;