rs7168025

Variant names:

• chr15-69056673-A-G
• rs7168025
• NM_024505.4:c.2275A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_024505.4(NOX5):​c.2275A>G​(p.Arg759Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,613,820 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0095 (27 hom., cov: 32)
  • Exomes 𝑓: 0.00097 (24 hom.)
• Consequence: NOX5 NM_024505.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.335
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003063202).
• BP6: Variant 15-69056673-A-G is Benign according to our data. Variant chr15-69056673-A-G is described in ClinVar as Benign. ClinVar VariationId is 785499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00946 (1440/152290) while in subpopulation AFR AF = 0.0334 (1389/41542). AF 95% confidence interval is 0.032. There are 27 homozygotes in GnomAd4. There are 675 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

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.2275A>G	p.Arg759Gly	missense	Exon 16 of 16	NP_078781.3
	NOX5	NM_001184779.2		c.2191A>G	p.Arg731Gly	missense	Exon 16 of 16	NP_001171708.1	Q96PH1-3
	SPESP1-NOX5	NM_001184780.2		c.2170A>G	p.Arg724Gly	missense	Exon 16 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.2275A>G	p.Arg759Gly	missense	Exon 16 of 16	ENSP00000373518.3	Q96PH1-1
	SPESP1-NOX5	ENST00000260364.9	TSL:1	c.2221A>G	p.Arg741Gly	missense	Exon 17 of 17	ENSP00000454143.1
	NOX5	ENST00000530406.7	TSL:1	c.2191A>G	p.Arg731Gly	missense	Exon 16 of 16	ENSP00000432440.2	Q96PH1-3

Frequencies

GnomAD3 genomes AF: 0.00946 AC: 1440 AN: 152172 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0335

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

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: 0.000103

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00251 AC: 631 AN: 251364 AF XY: 0.00188

Gnomad AFR exome AF: 0.0362

Gnomad AMR exome AF: 0.000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000974 AC: 1423 AN: 1461530 Hom.: 24 Cov.: 30 AF XY: 0.000858 AC XY: 624 AN XY: 727074

African (AFR) AF: 0.0369 AC: 1235 AN: 33474

American (AMR) AF: 0.00107 AC: 48 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

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

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000730 AC: 4 AN: 5478

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1112006

Other (OTH) AF: 0.00171 AC: 103 AN: 60368

GnomAD4 genome AF: 0.00946 AC: 1440 AN: 152290 Hom.: 27 Cov.: 32 AF XY: 0.00906 AC XY: 675 AN XY: 74470

African (AFR) AF: 0.0334 AC: 1389 AN: 41542

American (AMR) AF: 0.00209 AC: 32 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

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: 0.000103 AC: 7 AN: 68028

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00374 Hom.: 17

Bravo AF: 0.0104

ESP6500AA AF: 0.0325 AC: 143

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00306 AC: 372

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.76
DANN	Benign	0.22
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.018	N
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.34
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.084
Sift	Benign	0.38	T
Sift4G	Benign	0.30	T
Polyphen		0.15	B
Vest4		0.16
MVP		0.37
MPC		0.33
ClinPred		0.0071	T
GERP RS		0.52
Varity_R		0.053
gMVP		0.37
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs7168025; hg19: chr15-69349013;