Variant 15-69014774-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024505.4(NOX5):c.39A>T(p.Glu13Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,397,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NOX5
NM_024505.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.328

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05556667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOX5	NM_024505.4 linkuse as main transcript	c.39A>T	p.Glu13Asp	missense_variant	1/16	ENST00000388866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX5	ENST00000388866.8 linkuse as main transcript	c.39A>T	p.Glu13Asp	missense_variant	1/16	1	NM_024505.4		Q96PH1-1
NOX5	ENST00000530406.7 linkuse as main transcript	c.39A>T	p.Glu13Asp	missense_variant	1/16	1		P1	Q96PH1-3
NOX5	ENST00000527315.5 linkuse as main transcript	n.43A>T		non_coding_transcript_exon_variant	1/15	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000402

AC:

AN:

149330

Hom.:

AF XY:

0.0000622

AC XY:

AN XY:

80372

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000555

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1397422

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

689338

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

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

Apr 17, 2024

The c.39A>T (p.E13D) alteration is located in exon 1 (coding exon 1) of the NOX5 gene. This alteration results from a A to T substitution at nucleotide position 39, causing the glutamic acid (E) at amino acid position 13 to be replaced by an aspartic acid (D). 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

0.081

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.36

CADD

Benign

0.096

DANN

Benign

0.74

DEOGEN2

Benign

0.049

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.26

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-0.44

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.050

N;N

REVEL

Benign

0.20

Sift

Benign

0.48

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.0

B;B

Vest4

0.14

MutPred

0.27

Loss of helix (P = 0.028);Loss of helix (P = 0.028);

MVP

0.75

MPC

0.22

ClinPred

0.014

GERP RS

-2.9

Varity_R

0.040

gMVP

0.19

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over