chr6-155401355-T-G

Position:

• chr6-155401355-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015718.3(NOX3):​c.1581-4393A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 152,316 control chromosomes in the GnomAD database, including 88 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 0.023 (88 hom., cov: 32)
• Consequence: NOX3 NM_015718.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOX3	NM_015718.3	c.1581-4393A>C		intron_variant		ENST00000159060.3	NP_056533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOX3	ENST00000159060.3	c.1581-4393A>C		intron_variant		1	NM_015718.3	ENSP00000159060	P1

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3569 AN: 152198 Hom.: 86 Cov.: 32

Gnomad AFR AF: 0.0598

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00910

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00863

Gnomad OTH AF: 0.0230

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

GnomAD4 genome AF: 0.0235 AC: 3576 AN: 152316 Hom.: 88 Cov.: 32 AF XY: 0.0227 AC XY: 1694 AN XY: 74482

Gnomad4 AFR AF: 0.0598

Gnomad4 AMR AF: 0.0142

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00890

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00863

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0233 Hom.: 12

Bravo AF: 0.0269

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.4
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs10484602; hg19: chr6-155722489;