rs2073012

Variant names:

• chr6-155437101-C-T
• rs2073012
• NM_015718.3:c.669-554G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015718.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX3	NM_015718.3	MANE Select	c.669-554G>A		intron	N/A	NP_056533.1	Q9HBY0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX3	ENST00000159060.3	TSL:1 MANE Select	c.669-554G>A		intron	N/A	ENSP00000159060.2	Q9HBY0

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

African (AFR) AF: 0.449 AC: 18593 AN: 41432

American (AMR) AF: 0.292 AC: 4464 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1276 AN: 3464

East Asian (EAS) AF: 0.596 AC: 3065 AN: 5140

South Asian (SAS) AF: 0.341 AC: 1641 AN: 4814

European-Finnish (FIN) AF: 0.508 AC: 5362 AN: 10550

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22153 AN: 67944

Other (OTH) AF: 0.359 AC: 758 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.66
PhyloP100		-1.3
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: rs2073012; hg19: chr6-155758235; COSMIC: COSV50161806;