Genetic Variant ENOX1:p.Gln425Arg (chr13-43298518-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001347969.2(ENOX1):c.1274A>G(p.Gln425Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

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: 7.58

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.746

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.1274A>G	p.Gln425Arg	missense	Exon 12 of 17	NP_001334898.1	A0A024RDT8
ENOX1	NM_001347963.2		c.1379A>G	p.Gln460Arg	missense	Exon 11 of 16	NP_001334892.1
ENOX1	NM_001127615.3		c.1274A>G	p.Gln425Arg	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.1274A>G	p.Gln425Arg	missense	Exon 12 of 17	ENSP00000509229.1	Q8TC92-1
ENOX1	ENST00000261488.10	TSL:1	c.1274A>G	p.Gln425Arg	missense	Exon 12 of 17	ENSP00000261488.6	Q8TC92-1
ENOX1	ENST00000871211.1		c.1274A>G	p.Gln425Arg	missense	Exon 13 of 18	ENSP00000541270.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1458898

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725580

African (AFR)

AF:

0.00

AC:

AN:

33362

American (AMR)

AF:

0.00

AC:

AN:

44404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26076

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

85532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5274

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110986

Other (OTH)

AF:

0.00

AC:

AN:

60240

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

0.30

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.3

PhyloP100

7.6

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.9

REVEL

Benign

0.14

Sift

Benign

0.11

Sift4G

Benign

0.35

Polyphen

0.98

Vest4

0.78

MutPred

0.24

Gain of methylation at Q425 (P = 0.0384)

MVP

0.73

MPC

1.6

ClinPred

0.96

GERP RS

5.6

Varity_R

0.19

gMVP

0.25

Mutation Taster

=80/20

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over