rs12907196

chr15-69035886-C-T

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOX5	NM_024505.4	c.1138C>T	p.Leu380Phe	missense_variant	7/16	ENST00000388866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX5	ENST00000388866.8	c.1138C>T	p.Leu380Phe	missense_variant	7/16	1	NM_024505.4
NOX5	ENST00000530406.7	c.1054C>T	p.Leu352Phe	missense_variant	7/16	1		P1
NOX5	ENST00000525143.5	c.538C>T	p.Leu180Phe	missense_variant, NMD_transcript_variant	4/12	1
NOX5	ENST00000527315.5	n.4294C>T		non_coding_transcript_exon_variant	6/15	2

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

GnomAD3 exomes AF: 0.419 AC: 105384 AN: 251426 Hom.: 25524 AF XY: 0.430 AC XY: 58409 AN XY: 135888

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 SAS exome AF: 0.324

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

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.324

Gnomad4 FIN exome AF: 0.490

Gnomad4 NFE exome AF: 0.559

Gnomad4 OTH exome AF: 0.478

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

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.414

Alfa AF: 0.508 Hom.: 39815

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 v4.3

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
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.53	T;T;T;T;T
MetaRNN	Benign	0.00021	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.0029	P;P;P;P;P
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.3	N;N;N;N;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0070	D;D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D;D
Polyphen		0.30, 0.97, 0.89	.;.;B;D;P
Vest4		0.30
MPC		0.82
ClinPred		0.017	T
GERP RS		1.2
Varity_R		0.16
gMVP		0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs12907196; hg19: chr15-69328226; COSMIC: COSV52989754; COSMIC: COSV52989754;