rs311893

Positions:

• chr15-69033241-C-G
• chr15-69033241-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024505.4(NOX5):​c.819C>G​(p.Cys273Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NOX5 NM_024505.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOX5	NM_024505.4	c.819C>G	p.Cys273Trp	missense_variant	5/16	ENST00000388866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX5	ENST00000388866.8	c.819C>G	p.Cys273Trp	missense_variant	5/16	1	NM_024505.4
NOX5	ENST00000530406.7	c.735C>G	p.Cys245Trp	missense_variant	5/16	1		P1
NOX5	ENST00000525143.5	c.219C>G	p.Cys73Trp	missense_variant, NMD_transcript_variant	2/12	1
NOX5	ENST00000527315.5	n.3975C>G		non_coding_transcript_exon_variant	4/15	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 59

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	0.053
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.93	D;D;D;D;D
MetaSVM	Uncertain	0.60	D
MutationTaster	Benign	2.0e-9	P;P;P;P;P
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-7.9	D;D;D;D;D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D
Polyphen		1.0	.;.;D;D;D
Vest4		0.74
MutPred		0.81		.;.;.;Gain of catalytic residue at M268 (P = 0.0176);.;
MVP		1.0
MPC		1.0
ClinPred		1.0	D
GERP RS		-2.3
Varity_R		0.95
gMVP		0.86

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

LitVar

Other links and lift over

dbSNP: rs311893; hg19: chr15-69325581;