15-69026557-G-C

Position:

• chr15-69026557-G-C

Variant summary

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

The NM_024505.4(NOX5):​c.80G>C​(p.Trp27Ser) variant causes a missense change involving the alteration of a 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: 7.89

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.80G>C	p.Trp27Ser	missense_variant	2/16	ENST00000388866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX5	ENST00000388866.8	c.80G>C	p.Trp27Ser	missense_variant	2/16	1	NM_024505.4
NOX5	ENST00000530406.7	c.80G>C	p.Trp27Ser	missense_variant	2/16	1		P1
NOX5	ENST00000527315.5	n.84G>C		non_coding_transcript_exon_variant	2/15	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jun 13, 2022

The c.80G>C (p.W27S) alteration is located in exon 2 (coding exon 2) of the NOX5 gene. This alteration results from a G to C substitution at nucleotide position 80, causing the tryptophan (W) at amino acid position 27 to be replaced by a serine (S). 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	0.81
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Benign	0.95
DEOGEN2	Benign	0.31	.;.;.;T;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.81	T;T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.50	T;T;T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.8	.;.;.;L;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.3	D;D;D;D;D
REVEL	Uncertain	0.40
Sift	Benign	0.83	T;T;T;T;T
Sift4G	Benign	0.61	T;T;T;T;T
Polyphen		0.99, 0.99	.;.;D;D;D
Vest4		0.71
MutPred		0.54		.;.;.;Gain of disorder (P = 6e-04);Gain of disorder (P = 6e-04);
MVP		0.89
MPC		0.56
ClinPred		0.99	D
GERP RS		3.2
Varity_R		0.49
gMVP		0.84

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: chr15-69318897;