X-130656688-C-A

Variant names:

• chrX-130656688-C-A
• rs200580901
• NM_006375.4:c.1022G>T

Variant summary

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

The NM_006375.4(ENOX2):​c.1022G>T​(p.Arg341Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000102 in 978,376 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R341H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000010 (0 hom. 1 hem.)
• Consequence: ENOX2 NM_006375.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.59
• Publications: 0 publications found

Genes affected

ENOX2 (HGNC:2259): (ecto-NOX disulfide-thiol exchanger 2) This gene is a tumor-specific member of the ECTO-NOX family of genes that encode cell surface NADH oxidases. The encoded protein has two enzymatic activities: catalysis of hydroquinone or NADH oxidation, and protein disulfide interchange. The protein also displays prion-like properties. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

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_006375.4. 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
	ENOX2	NM_006375.4	MANE Select	c.1022G>T	p.Arg341Leu	missense	Exon 10 of 15	NP_006366.2
	ENOX2	NM_001382518.1		c.1298G>T	p.Arg433Leu	missense	Exon 11 of 16	NP_001369447.1	A0A8I5KRI1
	ENOX2	NM_001382516.1		c.1109G>T	p.Arg370Leu	missense	Exon 13 of 18	NP_001369445.1	Q16206-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOX2	ENST00000394363.6	TSL:2 MANE Select	c.1022G>T	p.Arg341Leu	missense	Exon 10 of 15	ENSP00000377890.1	Q16206-2
	ENOX2	ENST00000370927.5	TSL:1	c.1109G>T	p.Arg370Leu	missense	Exon 8 of 13	ENSP00000359965.1	Q16206-1
	ENOX2	ENST00000432489.5	TSL:1	c.1022G>T	p.Arg341Leu	missense	Exon 10 of 10	ENSP00000400304.1	B1AKF7

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00 AC: 0 AN: 166785 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 978376 Hom.: 0 Cov.: 19 AF XY: 0.00000362 AC XY: 1 AN XY: 276414

African (AFR) AF: 0.00 AC: 0 AN: 23541

American (AMR) AF: 0.00 AC: 0 AN: 32387

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18363

East Asian (EAS) AF: 0.0000342 AC: 1 AN: 29234

South Asian (SAS) AF: 0.00 AC: 0 AN: 48498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40199

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3847

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 740312

Other (OTH) AF: 0.00 AC: 0 AN: 41995

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	D
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.45	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.6
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.24
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.060	T
Polyphen		0.98	D
Vest4		0.88
MutPred		0.34		Loss of MoRF binding (P = 0.0363)
MVP		0.72
MPC		0.75
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.84
gMVP		0.58
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200580901; hg19: chrX-129790662;