rs231954

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015718.3(NOX3):​c.1038G>C​(p.Glu346Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 29)

Consequence

NOX3
NM_015718.3 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.157
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NOX3NM_015718.3 linkuse as main transcriptc.1038G>C p.Glu346Asp missense_variant 9/14 ENST00000159060.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NOX3ENST00000159060.3 linkuse as main transcriptc.1038G>C p.Glu346Asp missense_variant 9/141 NM_015718.3 P1

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD4 exome
Cov.:
60
GnomAD4 genome
Cov.:
29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.032
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.60
D
Eigen
Benign
-0.93
Eigen_PC
Benign
-0.78
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.044
D
MetaRNN
Uncertain
0.45
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.59
N
MutationTaster
Benign
0.073
P
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-2.5
N
REVEL
Benign
0.24
Sift
Benign
0.073
T
Sift4G
Benign
0.13
T
Polyphen
0.039
B
Vest4
0.23
MutPred
0.38
Gain of sheet (P = 0.1451);
MVP
0.79
MPC
0.054
ClinPred
0.54
D
GERP RS
0.0088
Varity_R
0.16
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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.

Other links and lift over

dbSNP: rs231954; hg19: chr6-155750035; API