15-69026607-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024505.4(NOX5):​c.130G>A​(p.Glu44Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

NOX5
NM_024505.4 missense

Scores

4
15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.13
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.025472969).
BP6
Variant 15-69026607-G-A is Benign according to our data. Variant chr15-69026607-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 743298.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NOX5NM_024505.4 linkuse as main transcriptc.130G>A p.Glu44Lys missense_variant 2/16 ENST00000388866.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NOX5ENST00000388866.8 linkuse as main transcriptc.130G>A p.Glu44Lys missense_variant 2/161 NM_024505.4 Q96PH1-1
NOX5ENST00000530406.7 linkuse as main transcriptc.130G>A p.Glu44Lys missense_variant 2/161 P1Q96PH1-3
NOX5ENST00000527315.5 linkuse as main transcriptn.134G>A non_coding_transcript_exon_variant 2/152

Frequencies

GnomAD3 genomes
AF:
0.00106
AC:
162
AN:
152220
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00359
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000785
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000215
AC:
54
AN:
251456
Hom.:
0
AF XY:
0.000162
AC XY:
22
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.00277
Gnomad AMR exome
AF:
0.000231
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000841
AC:
123
AN:
1461874
Hom.:
0
Cov.:
31
AF XY:
0.0000646
AC XY:
47
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00317
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.00108
AC:
164
AN:
152338
Hom.:
0
Cov.:
32
AF XY:
0.00110
AC XY:
82
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.00363
Gnomad4 AMR
AF:
0.000784
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000170
Hom.:
0
Bravo
AF:
0.00152
ESP6500AA
AF:
0.00386
AC:
17
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000198
AC:
24

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
.;.;.;T;.
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.33
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.83
T;T;T;T;T
M_CAP
Benign
0.0073
T
MetaRNN
Benign
0.025
T;T;T;T;T
MetaSVM
Benign
-0.78
T
MutationAssessor
Benign
1.9
.;.;.;L;L
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-2.6
D;D;D;D;D
REVEL
Benign
0.18
Sift
Uncertain
0.023
D;D;D;D;D
Sift4G
Uncertain
0.046
D;D;D;D;T
Polyphen
0.95, 0.91, 0.91
.;.;P;P;P
Vest4
0.40
MVP
0.76
MPC
0.29
ClinPred
0.074
T
GERP RS
0.90
Varity_R
0.27
gMVP
0.83

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.

Other links and lift over

dbSNP: rs147937844; hg19: chr15-69318947; COSMIC: COSV52989541; COSMIC: COSV52989541; API