chr15-69031619-C-G

Variant names:

• chr15-69031619-C-G
• rs78571685
• NM_024505.4:c.427C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024505.4(NOX5):​c.427C>G​(p.Pro143Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00568 in 1,613,222 control chromosomes in the GnomAD database, including 557 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0090 (56 hom., cov: 33)
  • Exomes 𝑓: 0.0053 (501 hom.)
• Consequence: NOX5 NM_024505.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015042424).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0668 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.427C>G	p.Pro143Ala	missense	Exon 4 of 16	NP_078781.3
	NOX5	NM_001184779.2		c.343C>G	p.Pro115Ala	missense	Exon 4 of 16	NP_001171708.1	Q96PH1-3
	SPESP1-NOX5	NM_001184780.2		c.322C>G	p.Pro108Ala	missense	Exon 4 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.427C>G	p.Pro143Ala	missense	Exon 4 of 16	ENSP00000373518.3	Q96PH1-1
	SPESP1-NOX5	ENST00000260364.9	TSL:1	c.373C>G	p.Pro125Ala	missense	Exon 5 of 17	ENSP00000454143.1
	NOX5	ENST00000530406.7	TSL:1	c.343C>G	p.Pro115Ala	missense	Exon 4 of 16	ENSP00000432440.2	Q96PH1-3

Frequencies

GnomAD3 genomes AF: 0.00904 AC: 1376 AN: 152236 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.00137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0702

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0377

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.0228 AC: 5687 AN: 249594 AF XY: 0.0174

Gnomad AFR exome AF: 0.000868

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0362

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.0147

GnomAD4 exome AF: 0.00533 AC: 7789 AN: 1460868 Hom.: 501 Cov.: 31 AF XY: 0.00461 AC XY: 3352 AN XY: 726834

African (AFR) AF: 0.00119 AC: 40 AN: 33478

American (AMR) AF: 0.131 AC: 5861 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26130

East Asian (EAS) AF: 0.0335 AC: 1328 AN: 39696

South Asian (SAS) AF: 0.00121 AC: 104 AN: 86252

European-Finnish (FIN) AF: 0.0000381 AC: 2 AN: 52514

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.000112 AC: 125 AN: 1111980

Other (OTH) AF: 0.00527 AC: 318 AN: 60386

GnomAD4 genome AF: 0.00903 AC: 1376 AN: 152354 Hom.: 56 Cov.: 33 AF XY: 0.00985 AC XY: 734 AN XY: 74512

African (AFR) AF: 0.00137 AC: 57 AN: 41588

American (AMR) AF: 0.0703 AC: 1076 AN: 15310

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

East Asian (EAS) AF: 0.0374 AC: 194 AN: 5182

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10630

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

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68024

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.00252 Hom.: 12

Bravo AF: 0.0152

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0175 AC: 2118

Asia WGS AF: 0.0210 AC: 74 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.10
DANN	Benign	0.56
DEOGEN2	Benign	0.092	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.44
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.099
Sift	Benign	0.51	T
Sift4G	Benign	0.51	T
Polyphen		0.0010	B
Vest4		0.22
MPC		0.23
ClinPred		0.0060	T
GERP RS		-4.8
Varity_R		0.046
gMVP		0.63
Mutation Taster		=98/2	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

Other links and lift over

dbSNP: rs78571685; hg19: chr15-69323959; COSMIC: COSV52988382; COSMIC: COSV52988382;