rs6926232

Positions:

• chr6-155402197-A-G
• chr6-155402197-A-T

Variant summary

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

The ENST00000159060.3(NOX3):​c.1580+4933T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,184 control chromosomes in the GnomAD database, including 2,214 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 0.17 (2214 hom., cov: 33)
• Consequence: NOX3 ENST00000159060.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOX3	NM_015718.3	c.1580+4933T>C		intron_variant		ENST00000159060.3	NP_056533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOX3	ENST00000159060.3	c.1580+4933T>C		intron_variant		1	NM_015718.3	ENSP00000159060	P1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25333 AN: 152066 Hom.: 2204 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.167 AC: 25358 AN: 152184 Hom.: 2214 Cov.: 33 AF XY: 0.172 AC XY: 12804 AN XY: 74418

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.177

Alfa AF: 0.167 Hom.: 285

Bravo AF: 0.165

Asia WGS AF: 0.238 AC: 827 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.3
DANN	Benign	0.57

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: rs6926232; hg19: chr6-155723331;