NM_007052.5:c.1078G>C

Variant names:

• chrX-100850206-C-G
• rs34688635
• NM_007052.5:c.1078G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_007052.5(NOX1):​c.1078G>C​(p.Asp360His) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,097,850 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: NOX1 NM_007052.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.27
• Publications: 0 publications found

Genes affected

NOX1 (HGNC:7889): (NADPH oxidase 1) This gene encodes a member of the NADPH oxidase family of enzymes responsible for the catalytic one-electron transfer of oxygen to generate superoxide or hydrogen peroxide. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.887

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007052.5. 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
	NOX1	NM_007052.5	MANE Select	c.1078G>C	p.Asp360His	missense	Exon 9 of 13	NP_008983.2	Q9Y5S8-1
	NOX1	NM_001271815.2		c.967G>C	p.Asp323His	missense	Exon 8 of 12	NP_001258744.1	A6NGA6
	NOX1	NM_013955.3		c.1078G>C	p.Asp360His	missense	Exon 9 of 12	NP_039249.1	Q9Y5S8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX1	ENST00000372966.8	TSL:1 MANE Select	c.1078G>C	p.Asp360His	missense	Exon 9 of 13	ENSP00000362057.3	Q9Y5S8-1
	NOX1	ENST00000372960.8	TSL:1	c.967G>C	p.Asp323His	missense	Exon 8 of 12	ENSP00000362051.4	A6NGA6
	NOX1	ENST00000217885.5	TSL:1	c.1078G>C	p.Asp360His	missense	Exon 9 of 12	ENSP00000217885.5	Q9Y5S8-3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097850 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363206

African (AFR) AF: 0.00 AC: 0 AN: 26396

American (AMR) AF: 0.00 AC: 0 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 54112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841810

Other (OTH) AF: 0.00 AC: 0 AN: 46085

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.91	D
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		4.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Pathogenic	0.86
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.57		Gain of helix (P = 0.132)
MVP		0.98
MPC		0.22
ClinPred		1.0	D
GERP RS		3.9
PromoterAI		0.0027	Neutral
Varity_R		0.93
gMVP		0.73
Mutation Taster		=46/54	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: rs34688635; hg19: chrX-100105195;