rs12661812

Variant names:

• chr6-155450463-C-T
• rs12661812
• NM_015718.3:c.340+2941G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.8).
• 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 rank	MANE	Protein	UniProt
NOX3	NM_015718.3	c.340+2941G>A		intron_variant	Intron 4 of 13	ENST00000159060.3	NP_056533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX3	ENST00000159060.3	c.340+2941G>A		intron_variant	Intron 4 of 13	1	NM_015718.3	ENSP00000159060.2

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

African (AFR) AF: 0.104 AC: 4305 AN: 41552

American (AMR) AF: 0.0708 AC: 1082 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0815 AC: 283 AN: 3472

East Asian (EAS) AF: 0.0195 AC: 101 AN: 5176

South Asian (SAS) AF: 0.0862 AC: 416 AN: 4826

European-Finnish (FIN) AF: 0.101 AC: 1068 AN: 10606

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0874 AC: 5946 AN: 68012

Other (OTH) AF: 0.0772 AC: 163 AN: 2112

Alfa AF: 0.0881 Hom.: 990

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
PhyloP100		0.14
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: rs12661812; hg19: chr6-155771597;