X-130656673-T-A

Variant names:

• chrX-130656673-T-A
• NM_006375.4:c.1037A>T

Variant summary

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

The NM_006375.4(ENOX2):​c.1037A>T​(p.Asp346Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ENOX2 NM_006375.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.39
• 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.1037A>T	p.Asp346Val	missense	Exon 10 of 15	NP_006366.2
	ENOX2	NM_001382518.1		c.1313A>T	p.Asp438Val	missense	Exon 11 of 16	NP_001369447.1	A0A8I5KRI1
	ENOX2	NM_001382516.1		c.1124A>T	p.Asp375Val	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.1037A>T	p.Asp346Val	missense	Exon 10 of 15	ENSP00000377890.1	Q16206-2
	ENOX2	ENST00000370927.5	TSL:1	c.1124A>T	p.Asp375Val	missense	Exon 8 of 13	ENSP00000359965.1	Q16206-1
	ENOX2	ENST00000432489.5	TSL:1	c.1037A>T	p.Asp346Val	missense	Exon 10 of 10	ENSP00000400304.1	B1AKF7

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 21

GnomAD4 genome Cov.: 23

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	0.58
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		7.4
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.24
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.92	P
Vest4		0.66
MutPred		0.32		Loss of catalytic residue at D375 (P = 0.0326)
MVP		0.85
MPC		0.60
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.76
gMVP		0.23
Mutation Taster		=71/29	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

hg19: chrX-129790647;