Variant 6-155440112-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015718.3(NOX3):c.512C>A(p.Thr171Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0791 in 1,602,040 control chromosomes in the GnomAD database, including 11,479 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.093 ( 1289 hom., cov: 32)

Exomes 𝑓: 0.078 ( 10190 hom. )

Consequence

NOX3
NM_015718.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.15

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062431395).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOX3	NM_015718.3 linkuse as main transcript	c.512C>A	p.Thr171Lys	missense_variant	6/14	ENST00000159060.3	NP_056533.1	Q9HBY0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOX3	ENST00000159060.3 linkuse as main transcript	c.512C>A	p.Thr171Lys	missense_variant	6/14	1	NM_015718.3	ENSP00000159060.2		Q9HBY0

Frequencies

GnomAD3 genomes

AF:

0.0931

AC:

14110

AN:

151600

Hom.:

1286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0739

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.0681

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0492

Gnomad OTH

AF:

0.0842

GnomAD3 exomes

AF:

0.136

AC:

32763

AN:

241652

Hom.:

4287

AF XY:

0.132

AC XY:

17177

AN XY:

130616

show subpopulations

Gnomad AFR exome

AF:

0.0718

Gnomad AMR exome

AF:

0.244

Gnomad ASJ exome

AF:

0.0666

Gnomad EAS exome

AF:

0.510

Gnomad SAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.116

Gnomad NFE exome

AF:

0.0486

Gnomad OTH exome

AF:

0.0964

GnomAD4 exome

AF:

0.0776

AC:

112565

AN:

1450322

Hom.:

10190

Cov.:

AF XY:

0.0802

AC XY:

57790

AN XY:

720916

show subpopulations

Gnomad4 AFR exome

AF:

0.0738

Gnomad4 AMR exome

AF:

0.234

Gnomad4 ASJ exome

AF:

0.0676

Gnomad4 EAS exome

AF:

0.513

Gnomad4 SAS exome

AF:

0.190

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.0458

Gnomad4 OTH exome

AF:

0.0885

GnomAD4 genome

AF:

0.0931

AC:

14120

AN:

151718

Hom.:

1289

Cov.:

AF XY:

0.103

AC XY:

7643

AN XY:

74118

show subpopulations

Gnomad4 AFR

AF:

0.0737

Gnomad4 AMR

AF:

0.157

Gnomad4 ASJ

AF:

0.0681

Gnomad4 EAS

AF:

0.501

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.0492

Gnomad4 OTH

AF:

0.0857

Alfa

AF:

0.0599

Hom.:

783

Bravo

AF:

0.0979

TwinsUK

AF:

0.0464

AC:

172

ALSPAC

AF:

0.0431

AC:

166

ESP6500AA

AF:

0.0710

AC:

313

ESP6500EA

AF:

0.0427

AC:

367

ExAC

AF:

0.127

AC:

15419

Asia WGS

AF:

0.324

AC:

1126

AN:

3478

EpiCase

AF:

0.0413

EpiControl

AF:

0.0427

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.53

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0062

MetaSVM

Pathogenic

0.84

MutationAssessor

Pathogenic

3.4

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.44

Sift

Benign

0.096

Sift4G

Benign

0.069

Polyphen

0.98

Vest4

0.28

MPC

0.35

ClinPred

0.073

GERP RS

5.8

Varity_R

0.58

gMVP

0.87

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over