rs138335737

Variant names:

• chr11-89354977-G-C
• NM_016931.5:c.1202C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-89354977-G-C
• chr11-89354977-G-T

Variant summary

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

The NM_016931.5(NOX4):​c.1202C>G​(p.Ser401Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000208 in 1,440,150 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NOX4 NM_016931.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.86

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX4	NM_016931.5	c.1202C>G	p.Ser401Cys	missense_variant	Exon 13 of 18	ENST00000263317.9	NP_058627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX4	ENST00000263317.9	c.1202C>G	p.Ser401Cys	missense_variant	Exon 13 of 18	1	NM_016931.5	ENSP00000263317.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1440150 Hom.: 0 Cov.: 24 AF XY: 0.00000279 AC XY: 2 AN XY: 717430

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: 0.00000274

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.32	.;.;.;T;.;.;.;.;.;.
Eigen	Benign	0.023
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.92	D;.;D;D;D;.;D;D;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.56	D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.79	D
MutationAssessor	Benign	0.99	.;.;L;L;.;.;.;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.4	N;N;N;N;N;N;N;N;N;N
REVEL	Uncertain	0.47
Sift	Uncertain	0.0090	D;D;T;D;T;D;T;D;T;T
Sift4G	Uncertain	0.042	D;D;T;D;T;D;T;T;T;T
Polyphen		0.031, 0.0060, 0.0010, 0.0030, 0.92, 0.017	.;.;B;B;.;.;B;B;P;B
Vest4		0.45
MutPred		0.74		.;.;Loss of disorder (P = 0.0319);Loss of disorder (P = 0.0319);.;.;.;.;.;.;
MVP		0.94
MPC		0.049
ClinPred		0.48	T
GERP RS		5.3
Varity_R		0.19
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr11-89088145;