rs2277552

chr15-69047447-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024505.4(NOX5):c.1727G>A(p.Arg576His) variant causes a missense change. The variant allele was found at a frequency of 0.0178 in 1,613,714 control chromosomes in the GnomAD database, including 1,642 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.048 (450 hom., cov: 32)
  • Exomes 𝑓: 0.015 (1192 hom.)
• Consequence: NOX5 NM_024505.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.50

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018219948).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOX5	NM_024505.4	c.1727G>A	p.Arg576His	missense_variant	12/16	ENST00000388866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX5	ENST00000388866.8	c.1727G>A	p.Arg576His	missense_variant	12/16	1	NM_024505.4

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 7353 AN: 152014 Hom.: 448 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0566

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0473

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00244

Gnomad OTH AF: 0.0511

GnomAD3 exomes AF: 0.0401 AC: 10063 AN: 250872 Hom.: 611 AF XY: 0.0343 AC XY: 4648 AN XY: 135538

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.0918

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.182

Gnomad SAS exome AF: 0.0111

Gnomad FIN exome AF: 0.0418

Gnomad NFE exome AF: 0.00275

Gnomad OTH exome AF: 0.0229

GnomAD4 exome AF: 0.0147 AC: 21425 AN: 1461582 Hom.: 1192 Cov.: 31 AF XY: 0.0139 AC XY: 10106 AN XY: 727094

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.0883

Gnomad4 ASJ exome AF: 0.00211

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.0102

Gnomad4 FIN exome AF: 0.0414

Gnomad4 NFE exome AF: 0.00156

Gnomad4 OTH exome AF: 0.0232

GnomAD4 genome AF: 0.0484 AC: 7367 AN: 152132 Hom.: 450 Cov.: 32 AF XY: 0.0500 AC XY: 3720 AN XY: 74362

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0563

Gnomad4 ASJ AF: 0.00289

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0473

Gnomad4 NFE AF: 0.00244

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0134 Hom.: 198

Bravo AF: 0.0557

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.113 AC: 496

ESP6500EA AF: 0.00291 AC: 25

ExAC AF: 0.0380 AC: 4610

Asia WGS AF: 0.0850 AC: 295 AN: 3478

EpiCase AF: 0.00185

EpiControl AF: 0.00267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Uncertain	0.010
Cadd	Uncertain	24
Dann	Pathogenic	1.0
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
MetaRNN	Benign	0.0018	T;T;T;T;T
MetaSVM	Benign	-1.3	T
MutationTaster	Benign	0.0000052	P;P;P;P;P
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.9	D;D;D;D;D
REVEL	Pathogenic	0.68
Sift	Benign	0.039	D;D;D;D;D
Sift4G	Uncertain	0.030	D;D;D;D;D
Polyphen		1.0, 1.0	.;.;D;D;D
Vest4		0.38
MPC		0.74
ClinPred		0.025	T
GERP RS		3.2
Varity_R		0.22
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs2277552; hg19: chr15-69339787; COSMIC: COSV52986445; COSMIC: COSV52986445;