Variant rs78571685 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024505.4(NOX5):c.427C>G(p.Pro143Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00568 in 1,613,222 control chromosomes in the GnomAD database, including 557 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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: 𝑓 0.0090 ( 56 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 501 hom. )

Consequence

NOX5
NM_024505.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.442

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=0.0015042424).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0668 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.427C>G	p.Pro143Ala	missense_variant	4/16	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.427C>G	p.Pro143Ala	missense_variant	4/16	1	NM_024505.4	ENSP00000373518		Q96PH1-1
NOX5	ENST00000530406.7 linkuse as main transcript	c.343C>G	p.Pro115Ala	missense_variant	4/16	1		ENSP00000432440	P1	Q96PH1-3
NOX5	ENST00000527315.5 linkuse as main transcript	n.3583C>G		non_coding_transcript_exon_variant	3/15	2

Frequencies

GnomAD3 genomes

AF:

0.00904

AC:

1376

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0702

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0377

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0228

AC:

5687

AN:

249594

Hom.:

395

AF XY:

0.0174

AC XY:

2356

AN XY:

135330

show subpopulations

Gnomad AFR exome

AF:

0.000868

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0362

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.0147

GnomAD4 exome

AF:

0.00533

AC:

7789

AN:

1460868

Hom.:

501

Cov.:

AF XY:

0.00461

AC XY:

3352

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.131

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0335

Gnomad4 SAS exome

AF:

0.00121

Gnomad4 FIN exome

AF:

0.0000381

Gnomad4 NFE exome

AF:

0.000112

Gnomad4 OTH exome

AF:

0.00527

GnomAD4 genome

AF:

0.00903

AC:

1376

AN:

152354

Hom.:

Cov.:

AF XY:

0.00985

AC XY:

734

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.0703

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0374

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00252

Hom.:

Bravo

AF:

0.0152

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0175

AC:

2118

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.10

DANN

Benign

0.56

DEOGEN2

Benign

0.092

.;.;.;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.75

T;T;T;T;T

MetaRNN

Benign

0.0015

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

.;.;.;L;.

MutationTaster

Benign

0.76

D;D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.5

N;N;N;N;N

REVEL

Benign

0.099

Sift

Benign

0.51

T;T;T;T;T

Sift4G

Benign

0.51

T;T;T;T;T

Polyphen

0.0010, 0.0

.;.;B;B;B

Vest4

0.22

MPC

0.23

ClinPred

0.0060

GERP RS

-4.8

Varity_R

0.046

gMVP

0.63

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