Variant chr13-43298357-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001347969.2(ENOX1):c.1435G>C(p.Gly479Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000926 in 1,608,444 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: 𝑓 0.00067 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00095 ( 0 hom. )

Consequence

ENOX1
NM_001347969.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82

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]

ENOX1 links:

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=0.13687345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENOX1	NM_001347969.2 linkuse as main transcript	c.1435G>C	p.Gly479Arg	missense_variant	12/17	ENST00000690772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENOX1	ENST00000690772.1 linkuse as main transcript	c.1435G>C	p.Gly479Arg	missense_variant	12/17		NM_001347969.2	P1	Q8TC92-1
ENOX1	ENST00000261488.10 linkuse as main transcript	c.1435G>C	p.Gly479Arg	missense_variant	12/17	1		P1	Q8TC92-1

Frequencies

GnomAD3 genomes

AF:

0.000672

AC:

101

AN:

150396

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000199

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000564

AC:

140

AN:

248292

Hom.:

AF XY:

0.000640

AC XY:

AN XY:

134276

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.000526

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.00102

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.000952

AC:

1388

AN:

1458048

Hom.:

Cov.:

AF XY:

0.000931

AC XY:

675

AN XY:

725224

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.000518

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.0000753

Gnomad4 NFE exome

AF:

0.00118

Gnomad4 OTH exome

AF:

0.000681

GnomAD4 genome

AF:

0.000672

AC:

101

AN:

150396

Hom.:

Cov.:

AF XY:

0.000642

AC XY:

AN XY:

73240

show subpopulations

Gnomad4 AFR

AF:

0.000170

Gnomad4 AMR

AF:

0.000199

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00134

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000863

Hom.:

Bravo

AF:

0.000680

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000453

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2024

The c.1435G>C (p.G479R) alteration is located in exon 12 (coding exon 9) of the ENOX1 gene. This alteration results from a G to C substitution at nucleotide position 1435, causing the glycine (G) at amino acid position 479 to be replaced by an arginine (R). 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

0.69

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.32

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.016

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.96

D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.060

Sift

Benign

0.068

Sift4G

Uncertain

0.011

Polyphen

0.42

Vest4

0.63

MVP

0.26

MPC

1.0

ClinPred

0.066

GERP RS

4.9

Varity_R

0.42

gMVP

0.25

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over