1-225828763-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001136018.4(EPHX1):​c.34G>A​(p.Gly12Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,613,360 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

EPHX1
NM_001136018.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.21
Variant links:
Genes affected
EPHX1 (HGNC:3401): (epoxide hydrolase 1) Epoxide hydrolase is a critical biotransformation enzyme that converts epoxides from the degradation of aromatic compounds to trans-dihydrodiols which can be conjugated and excreted from the body. Epoxide hydrolase functions in both the activation and detoxification of epoxides. Mutations in this gene cause preeclampsia, epoxide hydrolase deficiency or increased epoxide hydrolase activity. Alternatively spliced transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Dec 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EPHX1NM_001136018.4 linkuse as main transcriptc.34G>A p.Gly12Ser missense_variant 2/9 ENST00000272167.10 NP_001129490.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EPHX1ENST00000272167.10 linkuse as main transcriptc.34G>A p.Gly12Ser missense_variant 2/91 NM_001136018.4 ENSP00000272167 P1
EPHX1ENST00000366837.5 linkuse as main transcriptc.34G>A p.Gly12Ser missense_variant 2/91 ENSP00000355802 P1
EPHX1ENST00000614058.4 linkuse as main transcriptc.34G>A p.Gly12Ser missense_variant 2/91 ENSP00000480004 P1
EPHX1ENST00000448202.5 linkuse as main transcriptc.34G>A p.Gly12Ser missense_variant 2/42 ENSP00000408469

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151690
Hom.:
0
Cov.:
31
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
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251352
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135842
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461670
Hom.:
0
Cov.:
33
AF XY:
0.0000124
AC XY:
9
AN XY:
727118
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151690
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74050
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsOct 26, 2022The c.34G>A (p.G12S) alteration is located in exon 2 (coding exon 1) of the EPHX1 gene. This alteration results from a G to A substitution at nucleotide position 34, causing the glycine (G) at amino acid position 12 to be replaced by a serine (S). 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
Benign
0.18
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.43
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
.;T;.;T;T
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.72
T;.;T;T;.
M_CAP
Benign
0.013
T
MetaRNN
Uncertain
0.44
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
2.0
.;M;.;M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-3.1
D;D;D;.;D
REVEL
Benign
0.12
Sift
Benign
0.054
T;T;D;.;T
Sift4G
Benign
0.097
T;T;T;T;T
Polyphen
0.95
.;P;.;P;P
Vest4
0.22, 0.27, 0.21
MutPred
0.66
Gain of sheet (P = 0.0073);Gain of sheet (P = 0.0073);Gain of sheet (P = 0.0073);Gain of sheet (P = 0.0073);Gain of sheet (P = 0.0073);
MVP
0.32
MPC
0.25
ClinPred
0.87
D
GERP RS
2.9
Varity_R
0.090
gMVP
0.63

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.

Other links and lift over

dbSNP: rs770317327; hg19: chr1-226016464; API