rs1468425883

Variant names:

• chr11-89400364-A-C
• rs1468425883
• NM_016931.5:c.862T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-89400364-A-C
• chr11-89400364-A-G

Variant summary

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

The NM_016931.5(NOX4):​c.862T>G​(p.Ser288Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000091 in 1,429,300 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000091 (0 hom.)
• Consequence: NOX4 NM_016931.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.73
• Publications: 0 publications found

Genes affected

NOX4 (HGNC:7891): (NADPH oxidase 4) This gene encodes a member of the NOX-family of enzymes that functions as the catalytic subunit the NADPH oxidase complex. The encoded protein is localized to non-phagocytic cells where it acts as an oxygen sensor and catalyzes the reduction of molecular oxygen to various reactive oxygen species (ROS). The ROS generated by this protein have been implicated in numerous biological functions including signal transduction, cell differentiation and tumor cell growth. A pseudogene has been identified on the other arm of chromosome 11. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016931.5. 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
	NOX4	NM_016931.5	MANE Select	c.862T>G	p.Ser288Ala	missense	Exon 10 of 18	NP_058627.2	Q9NPH5-1
	NOX4	NM_001291927.1		c.925T>G	p.Ser309Ala	missense	Exon 10 of 18	NP_001278856.1	Q9NPH5
	NOX4	NM_001143837.2		c.790T>G	p.Ser264Ala	missense	Exon 13 of 21	NP_001137309.2	Q9NPH5-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX4	ENST00000263317.9	TSL:1 MANE Select	c.862T>G	p.Ser288Ala	missense	Exon 10 of 18	ENSP00000263317.4	Q9NPH5-1
	NOX4	ENST00000534731.5	TSL:1	c.862T>G	p.Ser288Ala	missense	Exon 10 of 17	ENSP00000436892.1	Q9NPH5-6
	NOX4	ENST00000525196.5	TSL:1	c.629+21538T>G		intron	N/A	ENSP00000436716.1	E9PI95

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000871 AC: 2 AN: 229580 AF XY: 0.00000805

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000910 AC: 13 AN: 1429300 Hom.: 0 Cov.: 33 AF XY: 0.0000113 AC XY: 8 AN XY: 709228

African (AFR) AF: 0.00 AC: 0 AN: 32298

American (AMR) AF: 0.00 AC: 0 AN: 38932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24740

East Asian (EAS) AF: 0.00 AC: 0 AN: 39160

South Asian (SAS) AF: 0.00 AC: 0 AN: 78506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 0.0000118 AC: 13 AN: 1098572

Other (OTH) AF: 0.00 AC: 0 AN: 58992

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	0.54	D
MutationAssessor	Benign	1.1	L
PhyloP100		6.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.32	N
REVEL	Uncertain	0.61
Sift	Benign	0.18	T
Sift4G	Benign	0.088	T
Polyphen		0.37	B
Vest4		0.63
MutPred		0.65		Loss of glycosylation at S288 (P = 0.0471)
MVP		0.93
MPC		0.070
ClinPred		0.52	D
GERP RS		5.2
Varity_R		0.12
gMVP		0.31
Mutation Taster		=35/65	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1468425883; hg19: chr11-89133532;