6-155428901-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_015718.3(NOX3):c.1038G>A(p.Glu346=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,613,178 control chromosomes in the GnomAD database, including 283,111 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 0.64 (31552 hom., cov: 29)
  • Exomes 𝑓: 0.58 (251559 hom.)
• Consequence: NOX3 NM_015718.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=0.157 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOX3	NM_015718.3	c.1038G>A	p.Glu346=	synonymous_variant	9/14	ENST00000159060.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX3	ENST00000159060.3	c.1038G>A	p.Glu346=	synonymous_variant	9/14	1	NM_015718.3	P1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96801 AN: 151700 Hom.: 31500 Cov.: 29

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.621

GnomAD3 exomes AF: 0.640 AC: 160599 AN: 250890 Hom.: 52769 AF XY: 0.637 AC XY: 86437 AN XY: 135638

Gnomad AFR exome AF: 0.720

Gnomad AMR exome AF: 0.665

Gnomad ASJ exome AF: 0.691

Gnomad EAS exome AF: 0.891

Gnomad SAS exome AF: 0.715

Gnomad FIN exome AF: 0.636

Gnomad NFE exome AF: 0.557

Gnomad OTH exome AF: 0.621

GnomAD4 exome AF: 0.581 AC: 848796 AN: 1461360 Hom.: 251559 Cov.: 60 AF XY: 0.585 AC XY: 425468 AN XY: 726976

Gnomad4 AFR exome AF: 0.714

Gnomad4 AMR exome AF: 0.661

Gnomad4 ASJ exome AF: 0.690

Gnomad4 EAS exome AF: 0.904

Gnomad4 SAS exome AF: 0.707

Gnomad4 FIN exome AF: 0.635

Gnomad4 NFE exome AF: 0.546

Gnomad4 OTH exome AF: 0.606

GnomAD4 genome AF: 0.638 AC: 96912 AN: 151818 Hom.: 31552 Cov.: 29 AF XY: 0.644 AC XY: 47772 AN XY: 74154

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.892

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.625

Alfa AF: 0.579 Hom.: 22547

Bravo AF: 0.637

Asia WGS AF: 0.823 AC: 2860 AN: 3478

EpiCase AF: 0.549

EpiControl AF: 0.553

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	5.5
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs231954; hg19: chr6-155750035; COSMIC: COSV50158747;