rs12907196

Variant names:

• chr15-69035886-C-T
• rs12907196
• NM_024505.4:c.1138C>T

Variant summary

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

The NM_024505.4(NOX5):​c.1138C>T​(p.Leu380Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,613,872 control chromosomes in the GnomAD database, including 213,252 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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 0.40 (14433 hom., cov: 32)
  • Exomes 𝑓: 0.51 (198819 hom.)
• Consequence: NOX5 NM_024505.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.496
• Publications: 26 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=2.07901E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.545 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.1138C>T	p.Leu380Phe	missense	Exon 7 of 16	NP_078781.3
	NOX5	NM_001184779.2		c.1054C>T	p.Leu352Phe	missense	Exon 7 of 16	NP_001171708.1	Q96PH1-3
	SPESP1-NOX5	NM_001184780.2		c.1033C>T	p.Leu345Phe	missense	Exon 7 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.1138C>T	p.Leu380Phe	missense	Exon 7 of 16	ENSP00000373518.3	Q96PH1-1
	SPESP1-NOX5	ENST00000260364.9	TSL:1	c.1084C>T	p.Leu362Phe	missense	Exon 8 of 17	ENSP00000454143.1
	NOX5	ENST00000530406.7	TSL:1	c.1054C>T	p.Leu352Phe	missense	Exon 7 of 16	ENSP00000432440.2	Q96PH1-3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60800 AN: 151954 Hom.: 14438 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.418

GnomAD2 exomes AF: 0.419 AC: 105384 AN: 251426 AF XY: 0.430

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.502

Gnomad EAS exome AF: 0.122

Gnomad FIN exome AF: 0.490

Gnomad NFE exome AF: 0.556

Gnomad OTH exome AF: 0.468

GnomAD4 exome AF: 0.508 AC: 742572 AN: 1461800 Hom.: 198819 Cov.: 55 AF XY: 0.505 AC XY: 367140 AN XY: 727202

African (AFR) AF: 0.163 AC: 5463 AN: 33472

American (AMR) AF: 0.269 AC: 12038 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 13166 AN: 26136

East Asian (EAS) AF: 0.118 AC: 4674 AN: 39700

South Asian (SAS) AF: 0.324 AC: 27955 AN: 86256

European-Finnish (FIN) AF: 0.490 AC: 26179 AN: 53384

Middle Eastern (MID) AF: 0.442 AC: 2550 AN: 5766

European-Non Finnish (NFE) AF: 0.559 AC: 621684 AN: 1111970

Other (OTH) AF: 0.478 AC: 28863 AN: 60394

GnomAD4 genome AF: 0.400 AC: 60783 AN: 152072 Hom.: 14433 Cov.: 32 AF XY: 0.393 AC XY: 29181 AN XY: 74320

African (AFR) AF: 0.177 AC: 7340 AN: 41520

American (AMR) AF: 0.368 AC: 5626 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1768 AN: 3464

East Asian (EAS) AF: 0.119 AC: 615 AN: 5172

South Asian (SAS) AF: 0.322 AC: 1551 AN: 4820

European-Finnish (FIN) AF: 0.479 AC: 5059 AN: 10556

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37372 AN: 67936

Other (OTH) AF: 0.414 AC: 873 AN: 2110

Alfa AF: 0.489 Hom.: 53251

Bravo AF: 0.382

TwinsUK AF: 0.549 AC: 2036

ALSPAC AF: 0.539 AC: 2077

ESP6500AA AF: 0.172 AC: 756

ESP6500EA AF: 0.555 AC: 4772

ExAC AF: 0.423 AC: 51380

Asia WGS AF: 0.249 AC: 866 AN: 3478

EpiCase AF: 0.560

EpiControl AF: 0.561

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.00021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.50
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.30	B
Vest4		0.30
MPC		0.82
ClinPred		0.017	T
GERP RS		1.2
Varity_R		0.16
gMVP		0.65
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12907196; hg19: chr15-69328226; COSMIC: COSV52989754; COSMIC: COSV52989754;