15-69031619-C-A

Variant names:

• chr15-69031619-C-A
• NM_024505.4:c.427C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024505.4(NOX5):​c.427C>A​(p.Pro143Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NOX5 NM_024505.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10542956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX5	NM_024505.4	c.427C>A	p.Pro143Thr	missense_variant	Exon 4 of 16	ENST00000388866.8	NP_078781.3
NOX5	NM_001184779.2	c.343C>A	p.Pro115Thr	missense_variant	Exon 4 of 16		NP_001171708.1
SPESP1-NOX5	NM_001184780.2	c.322C>A	p.Pro108Thr	missense_variant	Exon 4 of 16		NP_001171709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX5	ENST00000388866.8	c.427C>A	p.Pro143Thr	missense_variant	Exon 4 of 16	1	NM_024505.4	ENSP00000373518.3
NOX5	ENST00000260364.9	c.373C>A	p.Pro125Thr	missense_variant	Exon 5 of 17	1		ENSP00000454143.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460878 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726836

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	1.4
DANN	Benign	0.75
DEOGEN2	Benign	0.11	.;.;.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.14	N
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.1	.;.;.;M;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.8	N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.39	T;T;T;T;T
Sift4G	Benign	0.39	T;T;T;T;T
Polyphen		0.35, 0.20	.;.;B;B;B
Vest4		0.42
MutPred		0.32		.;.;.;Loss of stability (P = 0.0254);.;
MVP		0.57
MPC		0.31
ClinPred		0.41	T
GERP RS		-4.8
Varity_R		0.084
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-69323959;