rs77073843

Variant names:

• chr15-69037058-C-A
• rs77073843
• NM_024505.4:c.1219C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-69037058-C-A
• chr15-69037058-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024505.4(NOX5):​c.1219C>A​(p.Leu407Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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: not found (cov: 31)
• Consequence: NOX5 NM_024505.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.426
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14924055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX5	NM_024505.4	c.1219C>A	p.Leu407Ile	missense_variant	Exon 8 of 16	ENST00000388866.8	NP_078781.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX5	ENST00000388866.8	c.1219C>A	p.Leu407Ile	missense_variant	Exon 8 of 16	1	NM_024505.4	ENSP00000373518.3
SPESP1-NOX5	ENST00000703585.1	c.1114C>A	p.Leu372Ile	missense_variant	Exon 8 of 16			ENSP00000515387.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	6.5
DANN	Benign	0.64
DEOGEN2	Benign	0.13	.;.;.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.72	T;T;T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.30	.;.;.;N;.
PhyloP100		0.43
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.040	N;N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.47	T;T;T;T;T
Sift4G	Benign	0.45	T;T;T;T;T
Polyphen		0.011, 0.026, 0.019	.;.;B;B;B
Vest4		0.26
MutPred		0.56		.;.;.;Loss of catalytic residue at L407 (P = 0.0055);.;
MVP		0.76
MPC		0.26
ClinPred		0.081	T
GERP RS		-0.014
Varity_R		0.12
gMVP		0.34

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

Other links and lift over

dbSNP: rs77073843; hg19: chr15-69329398;