6-155442374-G-T

Variant names:

• chr6-155442374-G-T
• rs6557421
• NM_015718.3:c.486+899C>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.486+899C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,208 control chromosomes in the GnomAD database, including 3,479 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 0.20 (3479 hom., cov: 33)
• Consequence: NOX3 NM_015718.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.820
• Publications: 12 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX3	NM_015718.3	c.486+899C>A		intron_variant	Intron 5 of 13	ENST00000159060.3	NP_056533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX3	ENST00000159060.3	c.486+899C>A		intron_variant	Intron 5 of 13	1	NM_015718.3	ENSP00000159060.2

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30764 AN: 152088 Hom.: 3472 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.202 AC: 30783 AN: 152208 Hom.: 3479 Cov.: 33 AF XY: 0.208 AC XY: 15498 AN XY: 74418

African (AFR) AF: 0.107 AC: 4444 AN: 41536

American (AMR) AF: 0.243 AC: 3723 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 977 AN: 3470

East Asian (EAS) AF: 0.344 AC: 1783 AN: 5180

South Asian (SAS) AF: 0.290 AC: 1399 AN: 4820

European-Finnish (FIN) AF: 0.267 AC: 2824 AN: 10578

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.218 AC: 14797 AN: 68014

Other (OTH) AF: 0.219 AC: 463 AN: 2114

Alfa AF: 0.211 Hom.: 5178

Bravo AF: 0.196

Asia WGS AF: 0.276 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.6
DANN	Benign	0.56
PhyloP100		0.82
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: rs6557421; hg19: chr6-155763508;