15-69033241-C-T

Position:

• chr15-69033241-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_024505.4(NOX5):​c.819C>T​(p.Cys273Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 1,597,274 control chromosomes in the GnomAD database, including 701,373 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.87 (58459 hom., cov: 33)
  • Exomes 𝑓: 0.94 (642914 hom.)
• Consequence: NOX5 NM_024505.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=-0.28 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOX5	NM_024505.4	c.819C>T	p.Cys273Cys	synonymous_variant	5/16	ENST00000388866.8	NP_078781.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOX5	ENST00000388866.8	c.819C>T	p.Cys273Cys	synonymous_variant	5/16	1	NM_024505.4	ENSP00000373518.3
NOX5	ENST00000260364.9	c.765C>T	p.Cys255Cys	synonymous_variant	6/17	1		ENSP00000454143.1

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131821 AN: 152154 Hom.: 58438 Cov.: 33

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.957

Gnomad OTH AF: 0.898

GnomAD3 exomes AF: 0.913 AC: 210611 AN: 230634 Hom.: 97073 AF XY: 0.918 AC XY: 116318 AN XY: 126660

Gnomad AFR exome AF: 0.665

Gnomad AMR exome AF: 0.941

Gnomad ASJ exome AF: 0.964

Gnomad EAS exome AF: 0.752

Gnomad SAS exome AF: 0.896

Gnomad FIN exome AF: 0.949

Gnomad NFE exome AF: 0.960

Gnomad OTH exome AF: 0.934

GnomAD4 exome AF: 0.941 AC: 1360188 AN: 1445002 Hom.: 642914 Cov.: 59 AF XY: 0.941 AC XY: 676975 AN XY: 719204

Gnomad4 AFR exome AF: 0.651

Gnomad4 AMR exome AF: 0.939

Gnomad4 ASJ exome AF: 0.962

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 0.897

Gnomad4 FIN exome AF: 0.950

Gnomad4 NFE exome AF: 0.960

Gnomad4 OTH exome AF: 0.925

GnomAD4 genome AF: 0.866 AC: 131883 AN: 152272 Hom.: 58459 Cov.: 33 AF XY: 0.866 AC XY: 64516 AN XY: 74456

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.935

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.895

Gnomad4 FIN AF: 0.946

Gnomad4 NFE AF: 0.957

Gnomad4 OTH AF: 0.897

Alfa AF: 0.942 Hom.: 67299

Bravo AF: 0.856

Asia WGS AF: 0.802 AC: 2790 AN: 3478

EpiCase AF: 0.961

EpiControl AF: 0.962

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	5.4
DANN	Benign	0.93

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

LitVar

Other links and lift over

dbSNP: rs311893; hg19: chr15-69325581; COSMIC: COSV52986176; COSMIC: COSV52986176;