Variant 11-89354977-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016931.5(NOX4):c.1202C>A(p.Ser401Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000274 in 1,592,236 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

NOX4
NM_016931.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.86

Variant links:

Genes affected

NOX4 (HGNC:7891): (NADPH oxidase 4) This gene encodes a member of the NOX-family of enzymes that functions as the catalytic subunit the NADPH oxidase complex. The encoded protein is localized to non-phagocytic cells where it acts as an oxygen sensor and catalyzes the reduction of molecular oxygen to various reactive oxygen species (ROS). The ROS generated by this protein have been implicated in numerous biological functions including signal transduction, cell differentiation and tumor cell growth. A pseudogene has been identified on the other arm of chromosome 11. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2009]

NOX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26168314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOX4	NM_016931.5 link	c.1202C>A	p.Ser401Tyr	missense_variant	13/18	ENST00000263317.9	NP_058627.2	Q9NPH5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOX4	ENST00000263317.9 link	c.1202C>A	p.Ser401Tyr	missense_variant	13/18	1	NM_016931.5	ENSP00000263317.4		Q9NPH5-1

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000318

AC:

AN:

245540

Hom.:

AF XY:

0.000339

AC XY:

AN XY:

132922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000305

Gnomad ASJ exome

AF:

0.000699

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.0000932

Gnomad NFE exome

AF:

0.000563

Gnomad OTH exome

AF:

0.000341

GnomAD4 exome

AF:

0.000269

AC:

388

AN:

1440146

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

213

AN XY:

717426

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.000810

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000588

Gnomad4 FIN exome

AF:

0.000132

Gnomad4 NFE exome

AF:

0.000310

Gnomad4 OTH exome

AF:

0.000235

GnomAD4 genome

AF:

0.000316

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000933

Hom.:

Bravo

AF:

0.000246

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000363

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2023

The c.1202C>A (p.S401Y) alteration is located in exon 13 (coding exon 13) of the NOX4 gene. This alteration results from a C to A substitution at nucleotide position 1202, causing the serine (S) at amino acid position 401 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Benign

0.34

DEOGEN2

Benign

0.30

.;.;.;T;.;.;.;.;.;.

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.94

D;.;D;D;D;.;D;D;D;D

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.26

T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.78

MutationAssessor

Benign

1.3

.;.;L;L;.;.;.;.;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.4

N;N;N;N;N;N;D;N;N;N

REVEL

Uncertain

0.55

Sift

Uncertain

0.0060

D;D;T;D;T;D;D;T;T;T

Sift4G

Benign

0.067

T;T;T;T;T;T;T;T;T;T

Polyphen

0.061, 0.39, 0.27, 0.16, 0.76, 0.89

.;.;B;B;.;.;B;B;P;P

Vest4

0.53

MVP

0.95

MPC

0.085

ClinPred

0.045

GERP RS

5.3

Varity_R

0.25

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over