dbSNP rs2277552: NOX5:p.Arg576His (chr15-69047447-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024505.4(NOX5):c.1727G>A(p.Arg576His) variant causes a missense change. The variant allele was found at a frequency of 0.0178 in 1,613,714 control chromosomes in the GnomAD database, including 1,642 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 0.048 ( 450 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1192 hom. )

Consequence

NOX5
NM_024505.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.50

Publications

17 publications found

Variant links:

Genes affected

NOX5 (HGNC:14874): (NADPH oxidase 5) This gene is predominantly expressed in the testis and lymphocyte-rich areas of spleen and lymph nodes. It encodes a calcium-dependen NADPH oxidase that generates superoxide, and functions as a calcium-dependent proton channel that may regulate redox-dependent processes in lymphocytes and spermatozoa. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

NOX5 links:

SPESP1-NOX5 (HGNC:):

SPESP1-NOX5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018219948).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX5	NM_024505.4 link	c.1727G>A	p.Arg576His	missense_variant	Exon 12 of 16	ENST00000388866.8	NP_078781.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX5	ENST00000388866.8 link	c.1727G>A	p.Arg576His	missense_variant	Exon 12 of 16	1	NM_024505.4	ENSP00000373518.3
SPESP1-NOX5	ENST00000703585.1 link	c.1622G>A	p.Arg541His	missense_variant	Exon 12 of 16			ENSP00000515387.1

Frequencies

GnomAD3 genomes

AF:

0.0484

AC:

7353

AN:

152014

Hom.:

448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0566

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.0473

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00244

Gnomad OTH

AF:

0.0511

GnomAD2 exomes

AF:

0.0401

AC:

10063

AN:

250872

AF XY:

0.0343

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.0918

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.0418

Gnomad NFE exome

AF:

0.00275

Gnomad OTH exome

AF:

0.0229

GnomAD4 exome

AF:

0.0147

AC:

21425

AN:

1461582

Hom.:

1192

Cov.:

AF XY:

0.0139

AC XY:

10106

AN XY:

727094

show subpopulations

African (AFR)

AF:

0.114

AC:

3824

AN:

33468

American (AMR)

AF:

0.0883

AC:

3945

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00211

AC:

AN:

26120

East Asian (EAS)

AF:

0.184

AC:

7320

AN:

39698

South Asian (SAS)

AF:

0.0102

AC:

876

AN:

86246

European-Finnish (FIN)

AF:

0.0414

AC:

2205

AN:

53286

Middle Eastern (MID)

AF:

0.0109

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00156

AC:

1738

AN:

1111934

Other (OTH)

AF:

0.0232

AC:

1399

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1071

2142

3212

4283

5354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.0484

AC:

7367

AN:

152132

Hom.:

450

Cov.:

AF XY:

0.0500

AC XY:

3720

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.113

AC:

4685

AN:

41492

American (AMR)

AF:

0.0563

AC:

861

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00289

AC:

AN:

3466

East Asian (EAS)

AF:

0.186

AC:

955

AN:

5136

South Asian (SAS)

AF:

0.0151

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0473

AC:

502

AN:

10610

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00244

AC:

166

AN:

67994

Other (OTH)

AF:

0.0511

AC:

108

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

319

638

956

1275

1594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0175

Hom.:

508

Bravo

AF:

0.0557

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.113

AC:

496

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.0380

AC:

4610

Asia WGS

AF:

0.0850

AC:

295

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.00267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.29

.;.;.;T;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

D;D;D;D;D

MetaRNN

Benign

0.0018

T;T;T;T;T

MetaSVM

Benign

-1.3

MutationAssessor

Uncertain

2.7

.;.;.;M;.

PhyloP100

6.5

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.9

D;D;D;D;D

REVEL

Pathogenic

0.68

Sift

Benign

0.039

D;D;D;D;D

Sift4G

Uncertain

0.030

D;D;D;D;D

Polyphen

1.0, 1.0

.;.;D;D;D

Vest4

0.38

MPC

0.74

ClinPred

0.025

GERP RS

3.2

Varity_R

0.22

gMVP

0.72

Mutation Taster

=93/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

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

Publications

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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