rs36036826

Positions:

• chr15-69028330-A-G
• chr15-69028330-A-T

Variant summary

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

The NM_024505.4(NOX5):​c.290A>G​(p.Lys97Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,388 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K97I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NOX5 NM_024505.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.74

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.290A>G	p.Lys97Arg	missense_variant	3/16	ENST00000388866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX5	ENST00000388866.8	c.290A>G	p.Lys97Arg	missense_variant	3/16	1	NM_024505.4
NOX5	ENST00000530406.7	c.290A>G	p.Lys97Arg	missense_variant	3/16	1		P1
NOX5	ENST00000527315.5	n.294A>G		non_coding_transcript_exon_variant	3/15	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248852 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134478

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000331

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459388 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725988

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	.;.;.;T;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.61	D;D;D;D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	2.0	.;.;.;M;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D
REVEL	Uncertain	0.30
Sift	Benign	0.064	T;T;T;T;T
Sift4G	Benign	0.075	T;T;T;T;T
Polyphen		0.98, 0.96, 0.98	.;.;D;D;D
Vest4		0.74
MutPred		0.44		.;.;.;Loss of ubiquitination at K97 (P = 0.0326);Loss of ubiquitination at K97 (P = 0.0326);
MVP		0.81
MPC		0.24
ClinPred		0.83	D
GERP RS		3.7
Varity_R		0.29
gMVP		0.65

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: rs36036826; hg19: chr15-69320670;