6-155441051-G-T

Variant names:

• chr6-155441051-G-T
• rs6557420
• NM_015718.3:c.487-914C>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.487-914C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,018 control chromosomes in the GnomAD database, including 14,716 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 0.43 (14716 hom., cov: 33)
• Consequence: NOX3 NM_015718.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX3	NM_015718.3	MANE Select	c.487-914C>A		intron	N/A	NP_056533.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX3	ENST00000159060.3	TSL:1 MANE Select	c.487-914C>A		intron	N/A	ENSP00000159060.2

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65486 AN: 151898 Hom.: 14698 Cov.: 33

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.431 AC: 65550 AN: 152018 Hom.: 14716 Cov.: 33 AF XY: 0.426 AC XY: 31682 AN XY: 74296

African (AFR) AF: 0.554 AC: 22971 AN: 41464

American (AMR) AF: 0.407 AC: 6213 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1399 AN: 3468

East Asian (EAS) AF: 0.350 AC: 1806 AN: 5160

South Asian (SAS) AF: 0.406 AC: 1950 AN: 4806

European-Finnish (FIN) AF: 0.306 AC: 3230 AN: 10566

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26552 AN: 67960

Other (OTH) AF: 0.420 AC: 886 AN: 2112

Alfa AF: 0.383 Hom.: 4780

Bravo AF: 0.441

Asia WGS AF: 0.378 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.070
DANN	Benign	0.24
PhyloP100		-1.4
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: rs6557420; hg19: chr6-155762185;