rs78158861

Variant names:

• chr15-69037056-T-C
• rs78158861
• NM_024505.4:c.1217T>C
• NOX5 p.Leu406Pro

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024505.4(NOX5):​c.1217T>C​(p.Leu406Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NOX5 NM_024505.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.59
• Publications: 1 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.928

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.1217T>C	p.Leu406Pro	missense	Exon 8 of 16	NP_078781.3
	NOX5	NM_001184779.2		c.1133T>C	p.Leu378Pro	missense	Exon 8 of 16	NP_001171708.1	Q96PH1-3
	SPESP1-NOX5	NM_001184780.2		c.1112T>C	p.Leu371Pro	missense	Exon 8 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.1217T>C	p.Leu406Pro	missense	Exon 8 of 16	ENSP00000373518.3	Q96PH1-1
	SPESP1-NOX5	ENST00000260364.9	TSL:1	c.1163T>C	p.Leu388Pro	missense	Exon 9 of 17	ENSP00000454143.1
	NOX5	ENST00000530406.7	TSL:1	c.1133T>C	p.Leu378Pro	missense	Exon 8 of 16	ENSP00000432440.2	Q96PH1-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.065
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Benign	1.2	L
PhyloP100		6.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.9	D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Varity_R		0.83
gMVP		0.90

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs78158861;

hg19: chr15-69329396;