chr15-69033137-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_024505.4(NOX5):​c.715C>A​(p.Leu239Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,569,486 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 2 hom. )

Consequence

NOX5
NM_024505.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.75
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 -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.28811657).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NOX5NM_024505.4 linkuse as main transcriptc.715C>A p.Leu239Met missense_variant 5/16 ENST00000388866.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NOX5ENST00000388866.8 linkuse as main transcriptc.715C>A p.Leu239Met missense_variant 5/161 NM_024505.4 Q96PH1-1
NOX5ENST00000530406.7 linkuse as main transcriptc.631C>A p.Leu211Met missense_variant 5/161 P1Q96PH1-3
NOX5ENST00000525143.5 linkuse as main transcriptc.115C>A p.Leu39Met missense_variant, NMD_transcript_variant 2/121
NOX5ENST00000527315.5 linkuse as main transcriptn.3871C>A non_coding_transcript_exon_variant 4/152

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000270
AC:
5
AN:
184876
Hom.:
0
AF XY:
0.0000397
AC XY:
4
AN XY:
100860
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000618
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000116
AC:
164
AN:
1417282
Hom.:
2
Cov.:
33
AF XY:
0.000102
AC XY:
72
AN XY:
702458
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000143
Gnomad4 OTH exome
AF:
0.000118
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152204
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000117
Hom.:
0
Bravo
AF:
0.0000680
ExAC
AF:
0.0000336
AC:
4

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 submitterclinical testingAmbry GeneticsDec 02, 2022The c.715C>A (p.L239M) alteration is located in exon 5 (coding exon 5) of the NOX5 gene. This alteration results from a C to A substitution at nucleotide position 715, causing the leucine (L) at amino acid position 239 to be replaced by a methionine (M). 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
0.17
BayesDel_addAF
Benign
-0.079
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.10
.;.;.;T;.
Eigen
Benign
-0.0073
Eigen_PC
Benign
-0.14
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.47
T;T;T;T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.29
T;T;T;T;T
MetaSVM
Uncertain
0.61
D
MutationAssessor
Uncertain
2.5
.;.;.;M;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-1.1
N;N;N;N;N
REVEL
Uncertain
0.52
Sift
Benign
0.14
T;T;T;T;T
Sift4G
Uncertain
0.034
D;D;D;D;D
Polyphen
0.88, 0.96, 0.93
.;.;P;D;P
Vest4
0.41
MutPred
0.42
.;.;.;Gain of catalytic residue at L239 (P = 0.013);.;
MVP
0.98
MPC
0.68
ClinPred
0.48
T
GERP RS
1.2
Varity_R
0.12
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs764548905; hg19: chr15-69325477; API