15-69035363-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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.672

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]

ACMG classification

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
NOX5	NM_024505.4	c.865C>T	p.Leu289Phe	missense_variant	6/16	ENST00000388866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX5	ENST00000388866.8	c.865C>T	p.Leu289Phe	missense_variant	6/16	1	NM_024505.4
NOX5	ENST00000530406.7	c.781C>T	p.Leu261Phe	missense_variant	6/16	1		P1
NOX5	ENST00000525143.5	c.265C>T	p.Leu89Phe	missense_variant, NMD_transcript_variant	3/12	1
NOX5	ENST00000527315.5	n.4021C>T		non_coding_transcript_exon_variant	5/15	2

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

The 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
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
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;