6-155405882-G-A

Variant names:

• chr6-155405882-G-A
• rs9322522
• NM_015718.3:c.1580+1248C>T

Variant summary

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

The NM_015718.3(NOX3):​c.1580+1248C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 152,220 control chromosomes in the GnomAD database, including 678 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 0.053 (678 hom., cov: 32)
• Consequence: NOX3 NM_015718.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.993
• Publications: 0 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX3	NM_015718.3	c.1580+1248C>T		intron_variant	Intron 12 of 13	ENST00000159060.3	NP_056533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX3	ENST00000159060.3	c.1580+1248C>T		intron_variant	Intron 12 of 13	1	NM_015718.3	ENSP00000159060.2

Frequencies

GnomAD3 genomes AF: 0.0531 AC: 8079 AN: 152102 Hom.: 674 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0228

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0376

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00241

Gnomad OTH AF: 0.0392

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

GnomAD4 genome AF: 0.0533 AC: 8113 AN: 152220 Hom.: 678 Cov.: 32 AF XY: 0.0523 AC XY: 3889 AN XY: 74426

African (AFR) AF: 0.174 AC: 7204 AN: 41502

American (AMR) AF: 0.0227 AC: 347 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0377 AC: 195 AN: 5176

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4818

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00241 AC: 164 AN: 68032

Other (OTH) AF: 0.0416 AC: 88 AN: 2116

Alfa AF: 0.0322 Hom.: 70

Bravo AF: 0.0594

Asia WGS AF: 0.0530 AC: 186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.7
DANN	Benign	0.78
PhyloP100		0.99
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: rs9322522; hg19: chr6-155727016;