Variant chr15-69035886-C-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_024505.4(NOX5):c.1138C>T(p.Leu380Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,613,872 control chromosomes in the GnomAD database, including 213,252 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.40 ( 14433 hom., cov: 32)

Exomes 𝑓: 0.51 ( 198819 hom. )

Consequence

NOX5
NM_024505.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.496

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=2.07901E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.545 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.1138C>T	p.Leu380Phe	missense_variant	7/16	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.1138C>T	p.Leu380Phe	missense_variant	7/16	1	NM_024505.4	ENSP00000373518		Q96PH1-1
NOX5	ENST00000530406.7 linkuse as main transcript	c.1054C>T	p.Leu352Phe	missense_variant	7/16	1		ENSP00000432440	P1	Q96PH1-3
NOX5	ENST00000525143.5 linkuse as main transcript	c.538C>T	p.Leu180Phe	missense_variant, NMD_transcript_variant	4/12	1		ENSP00000455703
NOX5	ENST00000527315.5 linkuse as main transcript	n.4294C>T		non_coding_transcript_exon_variant	6/15	2

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60800

AN:

151954

Hom.:

14438

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.507

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.550

Gnomad OTH

AF:

0.418

GnomAD3 exomes

AF:

0.419

AC:

105384

AN:

251426

Hom.:

25524

AF XY:

0.430

AC XY:

58409

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.502

Gnomad EAS exome

AF:

0.122

Gnomad SAS exome

AF:

0.324

Gnomad FIN exome

AF:

0.490

Gnomad NFE exome

AF:

0.556

Gnomad OTH exome

AF:

0.468

GnomAD4 exome

AF:

0.508

AC:

742572

AN:

1461800

Hom.:

198819

Cov.:

AF XY:

0.505

AC XY:

367140

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.269

Gnomad4 ASJ exome

AF:

0.504

Gnomad4 EAS exome

AF:

0.118

Gnomad4 SAS exome

AF:

0.324

Gnomad4 FIN exome

AF:

0.490

Gnomad4 NFE exome

AF:

0.559

Gnomad4 OTH exome

AF:

0.478

GnomAD4 genome

AF:

0.400

AC:

60783

AN:

152072

Hom.:

14433

Cov.:

AF XY:

0.393

AC XY:

29181

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.368

Gnomad4 ASJ

AF:

0.510

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.322

Gnomad4 FIN

AF:

0.479

Gnomad4 NFE

AF:

0.550

Gnomad4 OTH

AF:

0.414

Alfa

AF:

0.508

Hom.:

39815

Bravo

AF:

0.382

TwinsUK

AF:

0.549

AC:

2036

ALSPAC

AF:

0.539

AC:

2077

ESP6500AA

AF:

0.172

AC:

756

ESP6500EA

AF:

0.555

AC:

4772

ExAC

AF:

0.423

AC:

51380

Asia WGS

AF:

0.249

AC:

866

AN:

3478

EpiCase

AF:

0.560

EpiControl

AF:

0.561

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

.;.;.;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.53

T;T;T;T;T

MetaRNN

Benign

0.00021

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

.;.;.;M;.

MutationTaster

Benign

0.0029

P;P;P;P;P

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.3

N;N;N;N;N

REVEL

Uncertain

0.43

Sift

Uncertain

0.0070

D;D;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D;D

Polyphen

0.30, 0.97, 0.89

.;.;B;D;P

Vest4

0.30

MPC

0.82

ClinPred

0.017

GERP RS

1.2

Varity_R

0.16

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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