chr15-69035485-C-T

Variant names:

• chr15-69035485-C-T
• rs311889
• NM_024505.4:c.987C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_024505.4(NOX5):​c.987C>T​(p.Thr329Thr) 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 1,614,026 control chromosomes in the GnomAD database, including 708,616 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 (58444 hom., cov: 32)
  • Exomes 𝑓: 0.94 (650172 hom.)
• Consequence: NOX5 NM_024505.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.27
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-4.27 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: NM_024505.4. 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.987C>T	p.Thr329Thr	synonymous	Exon 6 of 16	NP_078781.3
	NOX5	NM_001184779.2		c.903C>T	p.Thr301Thr	synonymous	Exon 6 of 16	NP_001171708.1
	SPESP1-NOX5	NM_001184780.2		c.882C>T	p.Thr294Thr	synonymous	Exon 6 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.987C>T	p.Thr329Thr	synonymous	Exon 6 of 16	ENSP00000373518.3
	SPESP1-NOX5	ENST00000260364.9	TSL:1	c.933C>T	p.Thr311Thr	synonymous	Exon 7 of 17	ENSP00000454143.1
	NOX5	ENST00000530406.7	TSL:1	c.903C>T	p.Thr301Thr	synonymous	Exon 6 of 16	ENSP00000432440.2

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131783 AN: 152076 Hom.: 58423 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.895

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: 229047 AN: 250988 AF XY: 0.917

Gnomad AFR exome AF: 0.660

Gnomad AMR exome AF: 0.940

Gnomad ASJ exome AF: 0.963

Gnomad EAS exome AF: 0.751

Gnomad FIN exome AF: 0.944

Gnomad NFE exome AF: 0.960

Gnomad OTH exome AF: 0.932

GnomAD4 exome AF: 0.941 AC: 1375800 AN: 1461832 Hom.: 650172 Cov.: 57 AF XY: 0.941 AC XY: 684397 AN XY: 727222

African (AFR) AF: 0.650 AC: 21764 AN: 33478

American (AMR) AF: 0.939 AC: 41978 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 25139 AN: 26132

East Asian (EAS) AF: 0.751 AC: 29816 AN: 39698

South Asian (SAS) AF: 0.897 AC: 77381 AN: 86248

European-Finnish (FIN) AF: 0.948 AC: 50620 AN: 53418

Middle Eastern (MID) AF: 0.960 AC: 5536 AN: 5766

European-Non Finnish (NFE) AF: 0.960 AC: 1067707 AN: 1111976

Other (OTH) AF: 0.925 AC: 55859 AN: 60394

GnomAD4 genome AF: 0.866 AC: 131845 AN: 152194 Hom.: 58444 Cov.: 32 AF XY: 0.867 AC XY: 64488 AN XY: 74408

African (AFR) AF: 0.670 AC: 27809 AN: 41478

American (AMR) AF: 0.935 AC: 14310 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3328 AN: 3470

East Asian (EAS) AF: 0.755 AC: 3901 AN: 5166

South Asian (SAS) AF: 0.894 AC: 4315 AN: 4824

European-Finnish (FIN) AF: 0.946 AC: 10038 AN: 10610

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

European-Non Finnish (NFE) AF: 0.957 AC: 65093 AN: 68026

Other (OTH) AF: 0.897 AC: 1890 AN: 2108

Alfa AF: 0.935 Hom.: 98116

Bravo AF: 0.856

Asia WGS AF: 0.803 AC: 2793 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	-0.87
CADD	Benign	0.45
DANN	Benign	0.63
PhyloP100		-4.3
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: rs311889; hg19: chr15-69327825; COSMIC: COSV108070063; COSMIC: COSV108070063;