chr15-69028261-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_024505.4(NOX5):​c.221G>A​(p.Ser74Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000719 in 1,613,328 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000043 ( 1 hom. )

Consequence

NOX5
NM_024505.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.49
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 Uncertain_significance. Variant got 4 ACMG points.

PM1
In a binding_site (size 0) in uniprot entity NOX5_HUMAN
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NOX5NM_024505.4 linkuse as main transcriptc.221G>A p.Ser74Asn missense_variant 3/16 ENST00000388866.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NOX5ENST00000388866.8 linkuse as main transcriptc.221G>A p.Ser74Asn missense_variant 3/161 NM_024505.4 Q96PH1-1
NOX5ENST00000530406.7 linkuse as main transcriptc.221G>A p.Ser74Asn missense_variant 3/161 P1Q96PH1-3
NOX5ENST00000527315.5 linkuse as main transcriptn.225G>A non_coding_transcript_exon_variant 3/152

Frequencies

GnomAD3 genomes
AF:
0.000348
AC:
53
AN:
152184
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00123
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00
GnomAD3 exomes
AF:
0.000120
AC:
30
AN:
250550
Hom.:
0
AF XY:
0.000111
AC XY:
15
AN XY:
135432
show subpopulations
Gnomad AFR exome
AF:
0.00148
Gnomad AMR exome
AF:
0.000174
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:
0.00
GnomAD4 exome
AF:
0.0000431
AC:
63
AN:
1461026
Hom.:
1
Cov.:
31
AF XY:
0.0000440
AC XY:
32
AN XY:
726822
show subpopulations
Gnomad4 AFR exome
AF:
0.00120
Gnomad4 AMR exome
AF:
0.000157
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:
0.00000810
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000348
AC:
53
AN:
152302
Hom.:
0
Cov.:
32
AF XY:
0.000363
AC XY:
27
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00123
Gnomad4 AMR
AF:
0.000131
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:
0.00
Alfa
AF:
0.0000876
Hom.:
0
Bravo
AF:
0.000412
ESP6500AA
AF:
0.00114
AC:
5
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000123
AC:
15

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 GeneticsJan 19, 2024The c.221G>A (p.S74N) alteration is located in exon 3 (coding exon 3) of the NOX5 gene. This alteration results from a G to A substitution at nucleotide position 221, causing the serine (S) at amino acid position 74 to be replaced by an asparagine (N). 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
0.25
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.28
.;.;.;T;.
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.43
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.77
T;D;T;D;T
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.045
T;T;T;T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
1.2
.;.;.;L;L
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-2.3
N;N;N;N;N
REVEL
Benign
0.091
Sift
Benign
0.054
T;T;T;T;T
Sift4G
Uncertain
0.0040
D;D;D;D;D
Polyphen
0.096, 0.23, 0.20
.;.;B;B;B
Vest4
0.31
MVP
0.75
MPC
0.37
ClinPred
0.048
T
GERP RS
2.9
Varity_R
0.22
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.28
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.28
Position offset: -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: rs147117800; hg19: chr15-69320601; API