rs2073012

Positions:

• chr6-155437101-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.669-554G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 151,930 control chromosomes in the GnomAD database, including 11,514 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 0.38 (11514 hom., cov: 32)
• Consequence: NOX3 NM_015718.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOX3	NM_015718.3	c.669-554G>A		intron_variant		ENST00000159060.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX3	ENST00000159060.3	c.669-554G>A		intron_variant		1	NM_015718.3	P1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57750 AN: 151812 Hom.: 11504 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.380 AC: 57789 AN: 151930 Hom.: 11514 Cov.: 32 AF XY: 0.387 AC XY: 28727 AN XY: 74244

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.359

Alfa AF: 0.374 Hom.: 1939

Bravo AF: 0.369

Asia WGS AF: 0.473 AC: 1648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.66

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: rs2073012; hg19: chr6-155758235; COSMIC: COSV50161806;