6-155418790-C-T

Variant names:

• chr6-155418790-C-T
• rs231945
• NM_015718.3:c.1308+3904G>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.1308+3904G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,220 control chromosomes in the GnomAD database, including 2,147 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 0.10 (2147 hom., cov: 33)
• Consequence: NOX3 NM_015718.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 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.1308+3904G>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.1308+3904G>A		intron	N/A	ENSP00000159060.2	Q9HBY0

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15678 AN: 152102 Hom.: 2135 Cov.: 33

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0417

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.0389

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0163

Gnomad OTH AF: 0.0767

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

GnomAD4 genome AF: 0.103 AC: 15733 AN: 152220 Hom.: 2147 Cov.: 33 AF XY: 0.102 AC XY: 7591 AN XY: 74432

African (AFR) AF: 0.309 AC: 12831 AN: 41496

American (AMR) AF: 0.0416 AC: 636 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.0388 AC: 201 AN: 5180

South Asian (SAS) AF: 0.0307 AC: 148 AN: 4826

European-Finnish (FIN) AF: 0.0573 AC: 608 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0163 AC: 1110 AN: 68026

Other (OTH) AF: 0.0797 AC: 168 AN: 2108

Alfa AF: 0.0516 Hom.: 1227

Bravo AF: 0.110

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.018
DANN	Benign	0.41
PhyloP100		-2.1
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: rs231945; hg19: chr6-155739924;