X-130667694-T-C

Variant names:

• chrX-130667694-T-C
• rs1203509087
• NM_006375.4:c.743A>G

Variant summary

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

The NM_006375.4(ENOX2):​c.743A>G​(p.Glu248Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,097,020 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: ENOX2 NM_006375.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• 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.743A>G	p.Glu248Gly	missense	Exon 8 of 15	NP_006366.2
	ENOX2	NM_001382518.1		c.1019A>G	p.Glu340Gly	missense	Exon 9 of 16	NP_001369447.1	A0A8I5KRI1
	ENOX2	NM_001382516.1		c.830A>G	p.Glu277Gly	missense	Exon 11 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.743A>G	p.Glu248Gly	missense	Exon 8 of 15	ENSP00000377890.1	Q16206-2
	ENOX2	ENST00000370927.5	TSL:1	c.830A>G	p.Glu277Gly	missense	Exon 6 of 13	ENSP00000359965.1	Q16206-1
	ENOX2	ENST00000432489.5	TSL:1	c.743A>G	p.Glu248Gly	missense	Exon 8 of 10	ENSP00000400304.1	B1AKF7

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1097020 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 362382

African (AFR) AF: 0.00 AC: 0 AN: 26378

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19376

East Asian (EAS) AF: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.00 AC: 0 AN: 54121

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841002

Other (OTH) AF: 0.00 AC: 0 AN: 46068

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

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	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	D
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.86	P
Vest4		0.90
MutPred		0.33		Gain of MoRF binding (P = 0.0298)
MVP		0.69
MPC		0.65
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.75
gMVP		0.90
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1203509087; hg19: chrX-129801668;