15-69035397-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_024505.4(NOX5):c.899G>A(p.Trp300Ter) 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, single submitter B:1
• Conservation: PhyloP100: 5.84

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 -8 ACMG points.

• PM4: Stoplost variant in NM_024505.4 Downstream stopcodon found after 778 codons.
• BP6: Variant 15-69035397-G-A is Benign according to our data. Variant chr15-69035397-G-A is described in ClinVar as [Benign]. Clinvar id is 785498.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.078 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOX5	NM_024505.4	c.899G>A	p.Trp300Ter	stop_gained	6/16	ENST00000388866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX5	ENST00000388866.8	c.899G>A	p.Trp300Ter	stop_gained	6/16	1	NM_024505.4
NOX5	ENST00000530406.7	c.815G>A	p.Trp272Ter	stop_gained	6/16	1		P1
NOX5	ENST00000525143.5	c.299G>A	p.Trp100Ter	stop_gained, NMD_transcript_variant	3/12	1
NOX5	ENST00000527315.5	n.4055G>A		non_coding_transcript_exon_variant	5/15	2

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

GnomAD3 exomes AF: 0.00595 AC: 1494 AN: 251154 Hom.: 56 AF XY: 0.00438 AC XY: 595 AN XY: 135792

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 SAS 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

Gnomad4 AFR exome AF: 0.0854

Gnomad4 AMR exome AF: 0.00360

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000129

Gnomad4 OTH exome AF: 0.00454

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

Gnomad4 AFR AF: 0.0803

Gnomad4 AMR AF: 0.00575

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00493 Hom.: 44

Bravo AF: 0.0256

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0832 AC: 366

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00722 AC: 877

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	A;A;A;A;A
Vest4		0.74
GERP RS		3.6

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: rs34406284; hg19: chr15-69327737;