15-69047447-G-A

Variant names:

• chr15-69047447-G-A
• rs2277552
• NM_024505.4:c.1727G>A

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 17 publications found

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]

SPESP1-NOX5 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024505.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX5	NM_024505.4	MANE Select	c.1727G>A	p.Arg576His	missense	Exon 12 of 16	NP_078781.3
	NOX5	NM_001184779.2		c.1643G>A	p.Arg548His	missense	Exon 12 of 16	NP_001171708.1
	SPESP1-NOX5	NM_001184780.2		c.1622G>A	p.Arg541His	missense	Exon 12 of 16	NP_001171709.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX5	ENST00000388866.8	TSL:1 MANE Select	c.1727G>A	p.Arg576His	missense	Exon 12 of 16	ENSP00000373518.3
	SPESP1-NOX5	ENST00000260364.9	TSL:1	c.1673G>A	p.Arg558His	missense	Exon 13 of 17	ENSP00000454143.1
	NOX5	ENST00000530406.7	TSL:1	c.1643G>A	p.Arg548His	missense	Exon 12 of 16	ENSP00000432440.2

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

GnomAD2 exomes AF: 0.0401 AC: 10063 AN: 250872 AF XY: 0.0343

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 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

African (AFR) AF: 0.114 AC: 3824 AN: 33468

American (AMR) AF: 0.0883 AC: 3945 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00211 AC: 55 AN: 26120

East Asian (EAS) AF: 0.184 AC: 7320 AN: 39698

South Asian (SAS) AF: 0.0102 AC: 876 AN: 86246

European-Finnish (FIN) AF: 0.0414 AC: 2205 AN: 53286

Middle Eastern (MID) AF: 0.0109 AC: 63 AN: 5766

European-Non Finnish (NFE) AF: 0.00156 AC: 1738 AN: 1111934

Other (OTH) AF: 0.0232 AC: 1399 AN: 60382

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

African (AFR) AF: 0.113 AC: 4685 AN: 41492

American (AMR) AF: 0.0563 AC: 861 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00289 AC: 10 AN: 3466

East Asian (EAS) AF: 0.186 AC: 955 AN: 5136

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4824

European-Finnish (FIN) AF: 0.0473 AC: 502 AN: 10610

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00244 AC: 166 AN: 67994

Other (OTH) AF: 0.0511 AC: 108 AN: 2114

Alfa AF: 0.0175 Hom.: 508

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 v4.9

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
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.3	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		6.5
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.9	D
REVEL	Pathogenic	0.68
Sift	Benign	0.039	D
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.38
MPC		0.74
ClinPred		0.025	T
GERP RS		3.2
Varity_R		0.22
gMVP		0.72
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2277552; hg19: chr15-69339787; COSMIC: COSV52986445; COSMIC: COSV52986445;