chr11-89354977-G-T

Variant names:

• chr11-89354977-G-T
• rs138335737
• NM_016931.5:c.1202C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016931.5(NOX4):​c.1202C>A​(p.Ser401Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000274 in 1,592,236 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S401P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00032 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (1 hom.)
• Consequence: NOX4 NM_016931.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.86
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26168314).

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.1202C>A	p.Ser401Tyr	missense	Exon 13 of 18	NP_058627.2	Q9NPH5-1
	NOX4	NM_001291927.1		c.1265C>A	p.Ser422Tyr	missense	Exon 13 of 18	NP_001278856.1	Q9NPH5
	NOX4	NM_001143837.2		c.1130C>A	p.Ser377Tyr	missense	Exon 16 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.1202C>A	p.Ser401Tyr	missense	Exon 13 of 18	ENSP00000263317.4	Q9NPH5-1
	NOX4	ENST00000534731.5	TSL:1	c.1202C>A	p.Ser401Tyr	missense	Exon 13 of 17	ENSP00000436892.1	Q9NPH5-6
	NOX4	ENST00000375979.7	TSL:1	c.281C>A	p.Ser94Tyr	missense	Exon 4 of 9	ENSP00000365146.3	Q9NPH5-4

Frequencies

GnomAD3 genomes AF: 0.000316 AC: 48 AN: 152090 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000318 AC: 78 AN: 245540 AF XY: 0.000339

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000305

Gnomad ASJ exome AF: 0.000699

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000932

Gnomad NFE exome AF: 0.000563

Gnomad OTH exome AF: 0.000341

GnomAD4 exome AF: 0.000269 AC: 388 AN: 1440146 Hom.: 1 Cov.: 24 AF XY: 0.000297 AC XY: 213 AN XY: 717426

African (AFR) AF: 0.0000304 AC: 1 AN: 32942

American (AMR) AF: 0.0000228 AC: 1 AN: 43784

Ashkenazi Jewish (ASJ) AF: 0.000810 AC: 21 AN: 25936

East Asian (EAS) AF: 0.00 AC: 0 AN: 39170

South Asian (SAS) AF: 0.0000588 AC: 5 AN: 84986

European-Finnish (FIN) AF: 0.000132 AC: 7 AN: 53130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.000310 AC: 339 AN: 1094962

Other (OTH) AF: 0.000235 AC: 14 AN: 59518

GnomAD4 genome AF: 0.000316 AC: 48 AN: 152090 Hom.: 1 Cov.: 32 AF XY: 0.000283 AC XY: 21 AN XY: 74272

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000933 Hom.: 0

Bravo AF: 0.000246

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000363 AC: 44

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	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Benign	0.34
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.78	D
MutationAssessor	Benign	1.3	L
PhyloP100		3.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.4	N
REVEL	Uncertain	0.55
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.067	T
Polyphen		0.061	B
Vest4		0.53
MVP		0.95
MPC		0.085
ClinPred		0.045	T
GERP RS		5.3
Varity_R		0.25
gMVP		0.37
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs138335737; hg19: chr11-89088145;