Genetic Variant NOX3:p.Glu346Glu (chr6-155428901-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_015718.3(NOX3):c.1038G>A(p.Glu346Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,613,178 control chromosomes in the GnomAD database, including 283,111 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 0.64 ( 31552 hom., cov: 29)

Exomes 𝑓: 0.58 ( 251559 hom. )

Consequence

NOX3
NM_015718.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.157

Publications

19 publications found

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 was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP7

Synonymous conserved (PhyloP=0.157 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX3	NM_015718.3 link	c.1038G>A	p.Glu346Glu	synonymous_variant	Exon 9 of 14	ENST00000159060.3	NP_056533.1	Q9HBY0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX3	ENST00000159060.3 link	c.1038G>A	p.Glu346Glu	synonymous_variant	Exon 9 of 14	1	NM_015718.3	ENSP00000159060.2		Q9HBY0

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96801

AN:

151700

Hom.:

31500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.718

Gnomad AMI

AF:

0.612

Gnomad AMR

AF:

0.642

Gnomad ASJ

AF:

0.700

Gnomad EAS

AF:

0.892

Gnomad SAS

AF:

0.733

Gnomad FIN

AF:

0.654

Gnomad MID

AF:

0.602

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.621

GnomAD2 exomes

AF:

0.640

AC:

160599

AN:

250890

AF XY:

0.637

show subpopulations

Gnomad AFR exome

AF:

0.720

Gnomad AMR exome

AF:

0.665

Gnomad ASJ exome

AF:

0.691

Gnomad EAS exome

AF:

0.891

Gnomad FIN exome

AF:

0.636

Gnomad NFE exome

AF:

0.557

Gnomad OTH exome

AF:

0.621

GnomAD4 exome

AF:

0.581

AC:

848796

AN:

1461360

Hom.:

251559

Cov.:

AF XY:

0.585

AC XY:

425468

AN XY:

726976

show subpopulations

African (AFR)

AF:

0.714

AC:

23880

AN:

33468

American (AMR)

AF:

0.661

AC:

29558

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.690

AC:

18032

AN:

26122

East Asian (EAS)

AF:

0.904

AC:

35866

AN:

39684

South Asian (SAS)

AF:

0.707

AC:

60893

AN:

86154

European-Finnish (FIN)

AF:

0.635

AC:

33921

AN:

53414

Middle Eastern (MID)

AF:

0.594

AC:

3423

AN:

5766

European-Non Finnish (NFE)

AF:

0.546

AC:

606653

AN:

1111690

Other (OTH)

AF:

0.606

AC:

36570

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

19349

38698

58046

77395

96744

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17250

34500

51750

69000

86250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.638

AC:

96912

AN:

151818

Hom.:

31552

Cov.:

AF XY:

0.644

AC XY:

47772

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.719

AC:

29744

AN:

41392

American (AMR)

AF:

0.642

AC:

9808

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.700

AC:

2426

AN:

3466

East Asian (EAS)

AF:

0.892

AC:

4570

AN:

5122

South Asian (SAS)

AF:

0.733

AC:

3532

AN:

4820

European-Finnish (FIN)

AF:

0.654

AC:

6883

AN:

10518

Middle Eastern (MID)

AF:

0.613

AC:

179

AN:

292

European-Non Finnish (NFE)

AF:

0.558

AC:

37898

AN:

67916

Other (OTH)

AF:

0.625

AC:

1316

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1701

3402

5103

6804

8505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.579

Hom.:

25136

Bravo

AF:

0.637

Asia WGS

AF:

0.823

AC:

2860

AN:

3478

EpiCase

AF:

0.549

EpiControl

AF:

0.553

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.5

(source)

DANN

Benign

0.48

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over