Variant chr6-155428828-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015718.3(NOX3):c.1111G>A(p.Gly371Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000897 in 1,560,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

NOX3
NM_015718.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

Variant links:

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]

NOX3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028136075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOX3	NM_015718.3 linkuse as main transcript	c.1111G>A	p.Gly371Arg	missense_variant	9/14	ENST00000159060.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX3	ENST00000159060.3 linkuse as main transcript	c.1111G>A	p.Gly371Arg	missense_variant	9/14	1	NM_015718.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000774

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000399

AC:

AN:

225478

Hom.:

AF XY:

0.0000411

AC XY:

AN XY:

121606

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000522

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000710

AC:

AN:

1408750

Hom.:

Cov.:

AF XY:

0.00000576

AC XY:

AN XY:

694104

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000234

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000775

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.1111G>A (p.G371R) alteration is located in exon 9 (coding exon 9) of the NOX3 gene. This alteration results from a G to A substitution at nucleotide position 1111, causing the glycine (G) at amino acid position 371 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.19

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.75

M_CAP

Benign

0.0052

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.66

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.36

REVEL

Benign

0.017

Sift

Benign

0.40

Sift4G

Benign

0.43

Polyphen

0.0060

Vest4

0.17

MutPred

0.30

Gain of helix (P = 0.132);

MVP

0.43

MPC

0.070

ClinPred

0.039

GERP RS

2.8

Varity_R

0.047

gMVP

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over