chr15-69031619-C-T

Variant names:

• chr15-69031619-C-T
• rs78571685
• NM_024505.4:c.427C>T

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>T​(p.Pro143Ser) 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. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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=0.09493959).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX5	NM_024505.4	c.427C>T	p.Pro143Ser	missense_variant	Exon 4 of 16	ENST00000388866.8	NP_078781.3
NOX5	NM_001184779.2	c.343C>T	p.Pro115Ser	missense_variant	Exon 4 of 16		NP_001171708.1
SPESP1-NOX5	NM_001184780.2	c.322C>T	p.Pro108Ser	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>T	p.Pro143Ser	missense_variant	Exon 4 of 16	1	NM_024505.4	ENSP00000373518.3
NOX5	ENST00000260364.9	c.373C>T	p.Pro125Ser	missense_variant	Exon 5 of 17	1		ENSP00000454143.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249594 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135330

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460878 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 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: 0.00

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	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	1.3
DANN	Benign	0.84
DEOGEN2	Benign	0.10	.;.;.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.095	T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.1	.;.;.;M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.8	N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.40	T;T;T;T;T
Sift4G	Benign	0.40	T;T;T;T;T
Polyphen		0.22, 0.11	.;.;B;B;B
Vest4		0.42
MutPred		0.30		.;.;.;Loss of catalytic residue at P143 (P = 0.0823);.;
MVP		0.56
MPC		0.29
ClinPred		0.15	T
GERP RS		-4.8
Varity_R		0.061
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs78571685; hg19: chr15-69323959;