NM_001347969.2:c.1382A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ENOX1NM_001347969.2 linkc.1382A>G p.Glu461Gly missense_variant Exon 12 of 17 ENST00000690772.1 NP_001334898.1 Q8TC92-1A0A024RDT8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENOX1ENST00000690772.1 linkc.1382A>G p.Glu461Gly missense_variant Exon 12 of 17 NM_001347969.2 ENSP00000509229.1 Q8TC92-1
ENOX1ENST00000261488.10 linkc.1382A>G p.Glu461Gly missense_variant Exon 12 of 17 1 ENSP00000261488.6 Q8TC92-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251458
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135902
show subpopulations
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 SAS 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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000495
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
EpiCase
AF:
0.000164
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1382A>G (p.E461G) alteration is located in exon 12 (coding exon 9) of the ENOX1 gene. This alteration results from a A to G substitution at nucleotide position 1382, causing the glutamic acid (E) at amino acid position 461 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1225702108; hg19: chr13-43872546; API