15-69033241-C-T

Variant names:

• chr15-69033241-C-T
• rs311893
• NM_024505.4:c.819C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The ENST00000388866.8(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 ENST00000388866.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 15 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000388866.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX5	NM_024505.4	MANE Select	c.819C>T	p.Cys273Cys	synonymous	Exon 5 of 16	NP_078781.3
	NOX5	NM_001184779.2		c.735C>T	p.Cys245Cys	synonymous	Exon 5 of 16	NP_001171708.1
	SPESP1-NOX5	NM_001184780.2		c.714C>T	p.Cys238Cys	synonymous	Exon 5 of 16	NP_001171709.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX5	ENST00000388866.8	TSL:1 MANE Select	c.819C>T	p.Cys273Cys	synonymous	Exon 5 of 16	ENSP00000373518.3
	SPESP1-NOX5	ENST00000260364.9	TSL:1	c.765C>T	p.Cys255Cys	synonymous	Exon 6 of 17	ENSP00000454143.1
	NOX5	ENST00000530406.7	TSL:1	c.735C>T	p.Cys245Cys	synonymous	Exon 5 of 16	ENSP00000432440.2

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

GnomAD2 exomes AF: 0.913 AC: 210611 AN: 230634 AF XY: 0.918

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 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

African (AFR) AF: 0.651 AC: 21640 AN: 33220

American (AMR) AF: 0.939 AC: 41653 AN: 44350

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 25040 AN: 26022

East Asian (EAS) AF: 0.750 AC: 29682 AN: 39576

South Asian (SAS) AF: 0.897 AC: 76776 AN: 85560

European-Finnish (FIN) AF: 0.950 AC: 37263 AN: 39212

Middle Eastern (MID) AF: 0.960 AC: 5530 AN: 5758

European-Non Finnish (NFE) AF: 0.960 AC: 1066923 AN: 1111114

Other (OTH) AF: 0.925 AC: 55681 AN: 60190

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

African (AFR) AF: 0.670 AC: 27835 AN: 41534

American (AMR) AF: 0.935 AC: 14308 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3330 AN: 3472

East Asian (EAS) AF: 0.752 AC: 3889 AN: 5170

South Asian (SAS) AF: 0.895 AC: 4327 AN: 4832

European-Finnish (FIN) AF: 0.946 AC: 10043 AN: 10614

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.957 AC: 65093 AN: 68024

Other (OTH) AF: 0.897 AC: 1897 AN: 2116

Alfa AF: 0.932 Hom.: 84345

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	5.4
DANN	Benign	0.93
PhyloP100		-0.28
Mutation Taster		=99/1	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: rs311893; hg19: chr15-69325581; COSMIC: COSV52986176; COSMIC: COSV52986176;