X-130656688-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_006375.4(ENOX2):​c.1022G>A​(p.Arg341His) variant causes a missense change. The variant allele was found at a frequency of 0.000056 in 1,090,216 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.000057 (0 hom. 18 hem.)
• Consequence: ENOX2 NM_006375.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.27160817).
• BS2: High Hemizygotes in GnomAd4 at 3 gene

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>A	p.Arg341His	missense	Exon 10 of 15	NP_006366.2
	ENOX2	NM_001382518.1		c.1298G>A	p.Arg433His	missense	Exon 11 of 16	NP_001369447.1	A0A8I5KRI1
	ENOX2	NM_001382516.1		c.1109G>A	p.Arg370His	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>A	p.Arg341His	missense	Exon 10 of 15	ENSP00000377890.1	Q16206-2
	ENOX2	ENST00000370927.5	TSL:1	c.1109G>A	p.Arg370His	missense	Exon 8 of 13	ENSP00000359965.1	Q16206-1
	ENOX2	ENST00000432489.5	TSL:1	c.1022G>A	p.Arg341His	missense	Exon 10 of 10	ENSP00000400304.1	B1AKF7

Frequencies

GnomAD3 genomes AF: 0.0000447 AC: 5 AN: 111790 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000189

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000277

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000240 AC: 4 AN: 166785 AF XY: 0.0000362

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: 0.0000261

Gnomad OTH exome AF: 0.000246

GnomAD4 exome AF: 0.0000572 AC: 56 AN: 978371 Hom.: 0 Cov.: 19 AF XY: 0.0000651 AC XY: 18 AN XY: 276409

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: 0.00 AC: 0 AN: 29234

South Asian (SAS) AF: 0.0000206 AC: 1 AN: 48498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40198

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

European-Non Finnish (NFE) AF: 0.0000675 AC: 50 AN: 740309

Other (OTH) AF: 0.000119 AC: 5 AN: 41994

GnomAD4 genome AF: 0.0000447 AC: 5 AN: 111845 Hom.: 0 Cov.: 23 AF XY: 0.0000880 AC XY: 3 AN XY: 34093

African (AFR) AF: 0.00 AC: 0 AN: 30787

American (AMR) AF: 0.000189 AC: 2 AN: 10582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.000278 AC: 1 AN: 3603

South Asian (SAS) AF: 0.00 AC: 0 AN: 2638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6013

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53149

Other (OTH) AF: 0.00 AC: 0 AN: 1518

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000330 AC: 4

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	0.65
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.58	D
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.6
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.26
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.039	D
Polyphen		1.0	D
Vest4		0.38
MutPred		0.32		Loss of MoRF binding (P = 0.0315)
MVP		0.86
MPC		0.32
ClinPred		0.73	D
GERP RS		4.1
Varity_R		0.56
gMVP		0.40
Mutation Taster		=99/1	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;