X-130656688-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

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

Scores

3
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.59
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ENOX2NM_006375.4 linkc.1022G>A p.Arg341His missense_variant Exon 10 of 15 ENST00000394363.6 NP_006366.2 Q16206-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENOX2ENST00000394363.6 linkc.1022G>A p.Arg341His missense_variant Exon 10 of 15 2 NM_006375.4 ENSP00000377890.1 Q16206-2

Frequencies

GnomAD3 genomes
AF:
0.0000447
AC:
5
AN:
111790
Hom.:
0
Cov.:
23
AF XY:
0.0000882
AC XY:
3
AN XY:
34028
show subpopulations
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
GnomAD3 exomes
AF:
0.0000240
AC:
4
AN:
166785
Hom.:
0
AF XY:
0.0000362
AC XY:
2
AN XY:
55193
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:
0.0000645
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
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:
0.0000206
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000675
Gnomad4 OTH exome
AF:
0.000119
GnomAD4 genome
AF:
0.0000447
AC:
5
AN:
111845
Hom.:
0
Cov.:
23
AF XY:
0.0000880
AC XY:
3
AN XY:
34093
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000189
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000278
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000376
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

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

The c.1109G>A (p.R370H) alteration is located in exon 11 (coding exon 8) of the ENOX2 gene. This alteration results from a G to A substitution at nucleotide position 1109, causing the arginine (R) at amino acid position 370 to be replaced by a histidine (H). 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
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;D;.;T;T
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.93
.;.;D;D;D;D
M_CAP
Pathogenic
0.30
D
MetaRNN
Benign
0.27
T;T;T;T;T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
2.0
.;M;M;.;.;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-3.5
D;D;D;D;.;D
REVEL
Benign
0.26
Sift
Uncertain
0.023
D;D;D;D;.;D
Sift4G
Uncertain
0.039
D;D;D;D;D;.
Polyphen
1.0
.;D;D;.;.;.
Vest4
0.38
MutPred
0.32
.;Loss of MoRF binding (P = 0.0315);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

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs200580901; hg19: chrX-129790662; API