rs1225702108

Variant names:

• chr13-43298410-T-C
• rs1225702108
• NM_001347969.2:c.1382A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001347969.2(ENOX1):​c.1382A>G​(p.Glu461Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000383 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: ENOX1 NM_001347969.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79
• Publications: 0 publications found

Genes affected

ENOX1 (HGNC:25474): (ecto-NOX disulfide-thiol exchanger 1) The protein encoded by this gene is involved in plasma membrane electron transport pathways. The encoded protein has both a hydroquinone (NADH) oxidase activity and a protein disulfide-thiol interchange activity. The two activities cycle with a periodicity of 24 minutes, with one activity being at its peak when the other is at its lowest. [provided by RefSeq, Dec 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22023466).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347969.2. 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
	ENOX1	NM_001347969.2	MANE Select	c.1382A>G	p.Glu461Gly	missense	Exon 12 of 17	NP_001334898.1	A0A024RDT8
	ENOX1	NM_001347963.2		c.1487A>G	p.Glu496Gly	missense	Exon 11 of 16	NP_001334892.1
	ENOX1	NM_001127615.3		c.1382A>G	p.Glu461Gly	missense	Exon 12 of 17	NP_001121087.1	A0A024RDT8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOX1	ENST00000690772.1	MANE Select	c.1382A>G	p.Glu461Gly	missense	Exon 12 of 17	ENSP00000509229.1	Q8TC92-1
	ENOX1	ENST00000261488.10	TSL:1	c.1382A>G	p.Glu461Gly	missense	Exon 12 of 17	ENSP00000261488.6	Q8TC92-1
	ENOX1	ENST00000871211.1		c.1382A>G	p.Glu461Gly	missense	Exon 13 of 18	ENSP00000541270.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251458 AF XY: 0.0000147

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: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000383 AC: 56 AN: 1461860 Hom.: 0 Cov.: 35 AF XY: 0.0000289 AC XY: 21 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1112000

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 33

EpiCase AF: 0.000164

EpiControl AF: 0.00

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	Benign	0.11
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.8
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.15
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.055	T
Polyphen		0.82	P
Vest4		0.41
MutPred		0.21		Gain of helix (P = 0.0325)
MVP		0.40
MPC		0.80
ClinPred		0.91	D
GERP RS		5.2
Varity_R		0.28
gMVP		0.059
Mutation Taster		=65/35	polymorphism

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: rs1225702108; hg19: chr13-43872546;