15-69033145-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_024505.4(NOX5):āc.723C>Gā(p.Cys241Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000636 in 1,573,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000053 ( 0 hom., cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
NOX5
NM_024505.4 missense
NM_024505.4 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 1.59
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3081159).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOX5 | NM_024505.4 | c.723C>G | p.Cys241Trp | missense_variant | 5/16 | ENST00000388866.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOX5 | ENST00000388866.8 | c.723C>G | p.Cys241Trp | missense_variant | 5/16 | 1 | NM_024505.4 | ||
NOX5 | ENST00000530406.7 | c.639C>G | p.Cys213Trp | missense_variant | 5/16 | 1 | P1 | ||
NOX5 | ENST00000525143.5 | c.123C>G | p.Cys41Trp | missense_variant, NMD_transcript_variant | 2/12 | 1 | |||
NOX5 | ENST00000527315.5 | n.3879C>G | non_coding_transcript_exon_variant | 4/15 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152198Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000141 AC: 2AN: 1421310Hom.: 0 Cov.: 33 AF XY: 0.00000142 AC XY: 1AN XY: 704770
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74360
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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 18, 2024 | The c.723C>G (p.C241W) alteration is located in exon 5 (coding exon 5) of the NOX5 gene. This alteration results from a C to G substitution at nucleotide position 723, causing the cysteine (C) at amino acid position 241 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;.;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;.;.;M;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.97, 0.95
.;.;D;P;D
Vest4
MVP
MPC
0.68
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at