chr15-69035363-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024505.4(NOX5):​c.865C>T​(p.Leu289Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NOX5
NM_024505.4 missense

Scores

1
12
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.672
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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.865C>T p.Leu289Phe missense_variant 6/16 ENST00000388866.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NOX5ENST00000388866.8 linkuse as main transcriptc.865C>T p.Leu289Phe missense_variant 6/161 NM_024505.4 Q96PH1-1
NOX5ENST00000530406.7 linkuse as main transcriptc.781C>T p.Leu261Phe missense_variant 6/161 P1Q96PH1-3
NOX5ENST00000525143.5 linkuse as main transcriptc.265C>T p.Leu89Phe missense_variant, NMD_transcript_variant 3/121
NOX5ENST00000527315.5 linkuse as main transcriptn.4021C>T non_coding_transcript_exon_variant 5/152

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 GeneticsFeb 27, 2024The c.865C>T (p.L289F) alteration is located in exon 6 (coding exon 6) of the NOX5 gene. This alteration results from a C to T substitution at nucleotide position 865, causing the leucine (L) at amino acid position 289 to be replaced by a phenylalanine (F). 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
Pathogenic
0.64
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Benign
13
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.51
.;.;.;D;.
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.79
T;T;T;T;T
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.43
T;T;T;T;T
MetaSVM
Uncertain
0.34
D
MutationAssessor
Uncertain
2.6
.;.;.;M;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-3.3
D;D;D;D;D
REVEL
Uncertain
0.44
Sift
Uncertain
0.027
D;D;D;D;D
Sift4G
Uncertain
0.021
D;D;D;D;D
Polyphen
0.18, 0.65, 0.52
.;.;B;P;P
Vest4
0.27
MutPred
0.67
.;.;.;Gain of MoRF binding (P = 0.1026);.;
MVP
0.98
MPC
0.64
ClinPred
0.97
D
GERP RS
0.41
Varity_R
0.80
gMVP
0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-69327703; API