Genetic Variant NM_001347969.2:c.1282G>A (chr13-43298510-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001347969.2(ENOX1):c.1282G>A(p.Ala428Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,612,874 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ENOX1
NM_001347969.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

Publications

2 publications found

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 was made for transcript

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=0.19556019).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENOX1	NM_001347969.2	MANE Select	c.1282G>A	p.Ala428Thr	missense	Exon 12 of 17	NP_001334898.1	A0A024RDT8
ENOX1	NM_001347963.2		c.1387G>A	p.Ala463Thr	missense	Exon 11 of 16	NP_001334892.1
ENOX1	NM_001127615.3		c.1282G>A	p.Ala428Thr	missense	Exon 12 of 17	NP_001121087.1	A0A024RDT8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENOX1	ENST00000690772.1	MANE Select	c.1282G>A	p.Ala428Thr	missense	Exon 12 of 17	ENSP00000509229.1	Q8TC92-1
ENOX1	ENST00000261488.10	TSL:1	c.1282G>A	p.Ala428Thr	missense	Exon 12 of 17	ENSP00000261488.6	Q8TC92-1
ENOX1	ENST00000871211.1		c.1282G>A	p.Ala428Thr	missense	Exon 13 of 18	ENSP00000541270.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250644

AF XY:

0.00000738

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460708

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726588

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33428

American (AMR)

AF:

0.00

AC:

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

85994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5396

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111716

Other (OTH)

AF:

0.0000166

AC:

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.056

Eigen

Benign

0.019

Eigen_PC

Benign

0.18

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.010

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

5.8

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.4

REVEL

Benign

0.091

Sift

Benign

0.097

Sift4G

Benign

0.18

Polyphen

0.20

Vest4

0.35

MutPred

0.13

Gain of phosphorylation at A428 (P = 0.0344)

MVP

0.58

MPC

1.5

ClinPred

0.95

GERP RS

4.8

Varity_R

0.15

gMVP

0.099

Mutation Taster

=85/15

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over