dbSNP rs34406284: NOX5:p.Trp300* (chr15-69035397-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.84

Publications

9 publications found

Variant links:

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]

NOX5 links:

SPESP1-NOX5 (HGNC:):

SPESP1-NOX5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX5	NM_024505.4 link	c.899G>A	p.Trp300*	stop_gained	Exon 6 of 16	ENST00000388866.8	NP_078781.3	Q96PH1-1A3QRJ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX5	ENST00000388866.8 link	c.899G>A	p.Trp300*	stop_gained	Exon 6 of 16	1	NM_024505.4	ENSP00000373518.3		Q96PH1-1
SPESP1-NOX5	ENST00000703585.1 link	c.794G>A	p.Trp265*	stop_gained	Exon 6 of 16			ENSP00000515387.1		Q96PH1-6

Frequencies

GnomAD3 genomes

AF:

0.0228

AC:

3471

AN:

152198

Hom.:

137

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.00208

AC XY:

1509

AN XY:

727222

show subpopulations

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:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000129

AC:

144

AN:

1112006

Other (OTH)

AF:

0.00454

AC:

274

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

175

350

526

701

876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0228

AC:

3477

AN:

152316

Hom.:

137

Cov.:

AF XY:

0.0225

AC XY:

1674

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0803

AC:

3336

AN:

41558

American (AMR)

AF:

0.00575

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68038

Other (OTH)

AF:

0.0161

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

164

328

493

657

821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00902

Hom.:

100

Bravo

AF:

0.0256

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0832

AC:

366

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00722

AC:

877

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.52

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.80

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.87

PhyloP100

5.8

Vest4

0.74

GERP RS

3.6

Mutation Taster

=171/29

polymorphism (auto)

(source)

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

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rs34406284

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over