rs34406284

Variant names:

• chr15-69035397-G-A
• rs34406284
• NM_024505.4:c.899G>A
• NOX5 p.Trp300*

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_024505.4(NOX5):​c.899G>A​(p.Trp300*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0043 in 1,614,168 control chromosomes in the GnomAD database, including 274 homozygotes. Variant has been reported in ClinVar as Benign (★★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.023 (137 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (137 hom.)
• Consequence: NOX5 NM_024505.4 stop_gained
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.84
• Publications: 9 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 -16 ACMG points.

• BP6: Variant 15-69035397-G-A is Benign according to our data. Variant chr15-69035397-G-A is described in ClinVar as Benign. ClinVar VariationId is 785498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.078 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX5	NM_024505.4	MANE Select	c.899G>A	p.Trp300*	stop_gained	Exon 6 of 16	NP_078781.3
	NOX5	NM_001184779.2		c.815G>A	p.Trp272*	stop_gained	Exon 6 of 16	NP_001171708.1	Q96PH1-3
	SPESP1-NOX5	NM_001184780.2		c.794G>A	p.Trp265*	stop_gained	Exon 6 of 16	NP_001171709.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX5	ENST00000388866.8	TSL:1 MANE Select	c.899G>A	p.Trp300*	stop_gained	Exon 6 of 16	ENSP00000373518.3	Q96PH1-1
	SPESP1-NOX5	ENST00000260364.9	TSL:1	c.845G>A	p.Trp282*	stop_gained	Exon 7 of 17	ENSP00000454143.1
	NOX5	ENST00000530406.7	TSL:1	c.815G>A	p.Trp272*	stop_gained	Exon 6 of 16	ENSP00000432440.2	Q96PH1-3

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3471 AN: 152198 Hom.: 137 Cov.: 32

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.00595 AC: 1494 AN: 251154 AF XY: 0.00438

Gnomad AFR exome AF: 0.0831

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00237 AC: 3464 AN: 1461852 Hom.: 137 Cov.: 30 AF XY: 0.00208 AC XY: 1509 AN XY: 727222

African (AFR) AF: 0.0854 AC: 2860 AN: 33478

American (AMR) AF: 0.00360 AC: 161 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5768

European-Non Finnish (NFE) AF: 0.000129 AC: 144 AN: 1112006

Other (OTH) AF: 0.00454 AC: 274 AN: 60392

GnomAD4 genome AF: 0.0228 AC: 3477 AN: 152316 Hom.: 137 Cov.: 32 AF XY: 0.0225 AC XY: 1674 AN XY: 74478

African (AFR) AF: 0.0803 AC: 3336 AN: 41558

American (AMR) AF: 0.00575 AC: 88 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68038

Other (OTH) AF: 0.0161 AC: 34 AN: 2112

Alfa AF: 0.00902 Hom.: 100

Bravo AF: 0.0256

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Pathogenic	0.52
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Pathogenic	0.80
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.87	D
PhyloP100		5.8
Mutation Taster		=171/29	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs34406284;

hg19: chr15-69327737;