rs9371889

Variant names:

• chr6-155421512-A-G
• rs9371889
• NM_015718.3:c.1308+1182T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015718.3(NOX3):​c.1308+1182T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,088 control chromosomes in the GnomAD database, including 5,698 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5698 hom., cov: 32)
• Consequence: NOX3 NM_015718.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 2 publications found

Genes affected

NOX3 (HGNC:7890): (NADPH oxidase 3) This gene encodes a member of the NOX family of NADPH oxidases. These enzymes have the capacity to generate superoxide and other reactive oxygen species (ROS) and transport electrons across the plasma membrane. The ROS generated by family members have been implicated in numerous biological functions including host defense, posttranlational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. The protein encoded by this gene is expressed predominantly in the inner ear and is involved in the biogenesis of otoconia/otolith, which are crystalline structures of the inner ear involved in the perception of gravity.[provided by RefSeq, May 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX3	NM_015718.3	c.1308+1182T>C		intron_variant	Intron 10 of 13	ENST00000159060.3	NP_056533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX3	ENST00000159060.3	c.1308+1182T>C		intron_variant	Intron 10 of 13	1	NM_015718.3	ENSP00000159060.2

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40758 AN: 151970 Hom.: 5686 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0756

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.260

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.268 AC: 40813 AN: 152088 Hom.: 5698 Cov.: 32 AF XY: 0.267 AC XY: 19872 AN XY: 74340

African (AFR) AF: 0.311 AC: 12898 AN: 41456

American (AMR) AF: 0.243 AC: 3717 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3468

East Asian (EAS) AF: 0.0754 AC: 391 AN: 5184

South Asian (SAS) AF: 0.217 AC: 1046 AN: 4828

European-Finnish (FIN) AF: 0.288 AC: 3053 AN: 10584

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18264 AN: 67960

Other (OTH) AF: 0.258 AC: 545 AN: 2114

Alfa AF: 0.261 Hom.: 1837

Bravo AF: 0.269

Asia WGS AF: 0.158 AC: 553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.8
DANN	Benign	0.64
PhyloP100		0.0080
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9371889; hg19: chr6-155742646; COSMIC: COSV50149786;