Genetic Variant ENOX1:p.Val541Met (chr13-43236729-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.1621G>A(p.Val541Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENOX1
NM_001347969.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

Publications

0 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:

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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=0.23114988).

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.1621G>A	p.Val541Met	missense	Exon 15 of 17	NP_001334898.1	A0A024RDT8
ENOX1	NM_001347963.2		c.1726G>A	p.Val576Met	missense	Exon 14 of 16	NP_001334892.1
ENOX1	NM_001127615.3		c.1621G>A	p.Val541Met	missense	Exon 15 of 17	NP_001121087.1	A0A024RDT8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENOX1	ENST00000690772.1	MANE Select	c.1621G>A	p.Val541Met	missense	Exon 15 of 17	ENSP00000509229.1	Q8TC92-1
ENOX1	ENST00000261488.10	TSL:1	c.1621G>A	p.Val541Met	missense	Exon 15 of 17	ENSP00000261488.6	Q8TC92-1
ENOX1	ENST00000871211.1		c.1621G>A	p.Val541Met	missense	Exon 16 of 18	ENSP00000541270.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1418012

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705308

African (AFR)

AF:

0.00

AC:

AN:

30702

American (AMR)

AF:

0.00

AC:

AN:

31770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24530

East Asian (EAS)

AF:

0.00

AC:

AN:

37932

South Asian (SAS)

AF:

0.00

AC:

AN:

77512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098962

Other (OTH)

AF:

0.00

AC:

AN:

58398

GnomAD4 genome

Cov.:

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

0.094

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.83

M_CAP

Benign

0.010

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

3.3

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.79

REVEL

Benign

0.092

Sift

Benign

0.17

Sift4G

Benign

0.21

Polyphen

0.88

Vest4

0.30

MutPred

0.32

Gain of catalytic residue at N540 (P = 0.0014)

MVP

0.40

MPC

0.63

ClinPred

0.49

GERP RS

5.7

Varity_R

0.14

gMVP

0.22

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over