rs12661812

Positions:

• chr6-155450463-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015718.3(NOX3):​c.340+2941G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 152,244 control chromosomes in the GnomAD database, including 611 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 0.089 (611 hom., cov: 32)
• Consequence: NOX3 NM_015718.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOX3	NM_015718.3	c.340+2941G>A		intron_variant		ENST00000159060.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX3	ENST00000159060.3	c.340+2941G>A		intron_variant		1	NM_015718.3	P1

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13563 AN: 152126 Hom.: 609 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.0709

Gnomad ASJ AF: 0.0815

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.0861

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.0775

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

GnomAD4 genome AF: 0.0892 AC: 13574 AN: 152244 Hom.: 611 Cov.: 32 AF XY: 0.0908 AC XY: 6758 AN XY: 74446

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0708

Gnomad4 ASJ AF: 0.0815

Gnomad4 EAS AF: 0.0195

Gnomad4 SAS AF: 0.0862

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0874

Gnomad4 OTH AF: 0.0772

Alfa AF: 0.0877 Hom.: 763

Bravo AF: 0.0878

Asia WGS AF: 0.0570 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.6
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs12661812; hg19: chr6-155771597;