rs231939

Variant names:

• chr6-155413537-A-G
• rs231939
• NM_015718.3:c.1309-2177T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015718.3(NOX3):​c.1309-2177T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,868 control chromosomes in the GnomAD database, including 12,470 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 0.35 (12470 hom., cov: 31)
• Consequence: NOX3 NM_015718.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX3	NM_015718.3	c.1309-2177T>C		intron_variant	Intron 10 of 13	ENST00000159060.3	NP_056533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX3	ENST00000159060.3	c.1309-2177T>C		intron_variant	Intron 10 of 13	1	NM_015718.3	ENSP00000159060.2

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53328 AN: 151750 Hom.: 12426 Cov.: 31

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.352 AC: 53443 AN: 151868 Hom.: 12470 Cov.: 31 AF XY: 0.358 AC XY: 26546 AN XY: 74218

African (AFR) AF: 0.661 AC: 27333 AN: 41370

American (AMR) AF: 0.285 AC: 4355 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 737 AN: 3470

East Asian (EAS) AF: 0.463 AC: 2389 AN: 5156

South Asian (SAS) AF: 0.323 AC: 1554 AN: 4804

European-Finnish (FIN) AF: 0.325 AC: 3432 AN: 10544

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.187 AC: 12678 AN: 67940

Other (OTH) AF: 0.321 AC: 678 AN: 2110

Alfa AF: 0.297 Hom.: 1123

Bravo AF: 0.363

Asia WGS AF: 0.496 AC: 1721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.47
PhyloP100		-0.087
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: rs231939; hg19: chr6-155734671;