rs78571685

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr15-69031619-C-A
• chr15-69031619-C-G
• chr15-69031619-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.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. 14/22 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: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NOX5 NM_024505.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442
• 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=0.10542956).

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

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
SPESP1-NOX5	ENST00000703585.1	c.322C>A	p.Pro108Thr	missense_variant	Exon 4 of 16			ENSP00000515387.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111980

Other (OTH) AF: 0.00 AC: 0 AN: 60386

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;.
PhyloP100		0.44
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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs78571685; hg19: chr15-69323959;