Genetic Variant NOX5:p.Pro143Ser (chr15-69031619-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024505.4(NOX5):c.427C>T(p.Pro143Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NOX5
NM_024505.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.442

Publications

7 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09493959).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX5	NM_024505.4 link	c.427C>T	p.Pro143Ser	missense_variant	Exon 4 of 16	ENST00000388866.8	NP_078781.3	Q96PH1-1A3QRJ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX5	ENST00000388866.8 link	c.427C>T	p.Pro143Ser	missense_variant	Exon 4 of 16	1	NM_024505.4	ENSP00000373518.3		Q96PH1-1
SPESP1-NOX5	ENST00000703585.1 link	c.322C>T	p.Pro108Ser	missense_variant	Exon 4 of 16			ENSP00000515387.1		Q96PH1-6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249594

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726836

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111980

Other (OTH)

AF:

0.00

AC:

AN:

60386

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

1.3

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.10

.;.;.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.88

D;D;D;D;D

M_CAP

Benign

0.0028

MetaRNN

Benign

0.095

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.1

.;.;.;M;.

PhyloP100

0.44

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.8

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.40

T;T;T;T;T

Sift4G

Benign

0.40

T;T;T;T;T

Polyphen

0.22, 0.11

.;.;B;B;B

Vest4

0.42

MutPred

0.30

.;.;.;Loss of catalytic residue at P143 (P = 0.0823);.;

MVP

0.56

MPC

0.29

ClinPred

0.15

GERP RS

-4.8

Varity_R

0.061

gMVP

0.70

Mutation Taster

=97/3

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over