NM_015718.3:c.1308+4060A>C

Variant names:

• chr6-155418634-T-G
• rs231944
• NM_015718.3:c.1308+4060A>C

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+4060A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 139,700 control chromosomes in the GnomAD database, including 12,134 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 0.40 (12134 hom., cov: 27)
• Consequence: NOX3 NM_015718.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX3	NM_015718.3	c.1308+4060A>C		intron_variant	Intron 10 of 13	ENST00000159060.3	NP_056533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX3	ENST00000159060.3	c.1308+4060A>C		intron_variant	Intron 10 of 13	1	NM_015718.3	ENSP00000159060.2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 55858 AN: 139582 Hom.: 12090 Cov.: 27

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.401 AC: 55968 AN: 139700 Hom.: 12134 Cov.: 27 AF XY: 0.414 AC XY: 27770 AN XY: 67004

African (AFR) AF: 0.631 AC: 24758 AN: 39254

American (AMR) AF: 0.379 AC: 4545 AN: 12002

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 934 AN: 3348

East Asian (EAS) AF: 0.502 AC: 2372 AN: 4726

South Asian (SAS) AF: 0.380 AC: 1654 AN: 4350

European-Finnish (FIN) AF: 0.454 AC: 3864 AN: 8516

Middle Eastern (MID) AF: 0.299 AC: 73 AN: 244

European-Non Finnish (NFE) AF: 0.261 AC: 16801 AN: 64450

Other (OTH) AF: 0.369 AC: 713 AN: 1932

Alfa AF: 0.311 Hom.: 1855

Bravo AF: 0.378

Asia WGS AF: 0.506 AC: 1757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.85
DANN	Benign	0.34
PhyloP100		-0.51
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: rs231944; hg19: chr6-155739768; COSMIC: COSV50149763;