6-155450116-G-C

Variant names:

• chr6-155450116-G-C
• rs7754577
• NM_015718.3:c.340+3288C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015718.3(NOX3):​c.340+3288C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,152 control chromosomes in the GnomAD database, including 3,421 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 (3421 hom., cov: 32)
• Consequence: NOX3 NM_015718.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 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.340+3288C>G		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.340+3288C>G		intron	N/A	ENSP00000159060.2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30064 AN: 152034 Hom.: 3416 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0367

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.198 AC: 30097 AN: 152152 Hom.: 3421 Cov.: 32 AF XY: 0.196 AC XY: 14596 AN XY: 74370

African (AFR) AF: 0.310 AC: 12874 AN: 41504

American (AMR) AF: 0.153 AC: 2344 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 735 AN: 3470

East Asian (EAS) AF: 0.0368 AC: 190 AN: 5166

South Asian (SAS) AF: 0.148 AC: 713 AN: 4816

European-Finnish (FIN) AF: 0.145 AC: 1536 AN: 10592

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11095 AN: 67992

Other (OTH) AF: 0.195 AC: 412 AN: 2112

Alfa AF: 0.179 Hom.: 328

Bravo AF: 0.204

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.58
PhyloP100		-0.96
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: rs7754577; hg19: chr6-155771250; COSMIC: COSV50161828;