Variant 15-69047447-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000388866.8(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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.048 ( 450 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1192 hom. )

Consequence

NOX5
ENST00000388866.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.50

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NOX5	NM_024505.4 linkuse as main transcript	c.1727G>A	p.Arg576His	missense_variant	12/16	ENST00000388866.8	NP_078781.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOX5	ENST00000388866.8 linkuse as main transcript	c.1727G>A	p.Arg576His	missense_variant	12/16	1	NM_024505.4	ENSP00000373518		Q96PH1-1

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

GnomAD3 exomes

AF:

0.0401

AC:

10063

AN:

250872

Hom.:

611

AF XY:

0.0343

AC XY:

4648

AN XY:

135538

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 SAS exome

AF:

0.0111

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

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.0883

Gnomad4 ASJ exome

AF:

0.00211

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.0414

Gnomad4 NFE exome

AF:

0.00156

Gnomad4 OTH exome

AF:

0.0232

GnomAD4 genome

AF:

0.0484

AC:

7367

AN:

152132

Hom.:

450

Cov.:

AF XY:

0.0500

AC XY:

3720

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.113

Gnomad4 AMR

AF:

0.0563

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.186

Gnomad4 SAS

AF:

0.0151

Gnomad4 FIN

AF:

0.0473

Gnomad4 NFE

AF:

0.00244

Gnomad4 OTH

AF:

0.0511

Alfa

AF:

0.0134

Hom.:

198

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

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;.

MutationTaster

Benign

0.0000052

P;P;P;P;P

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

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

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