1-225828763-G-A
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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
NM_001136018.4 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 4.21
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]
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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 |
---|---|---|---|---|---|---|---|---|
EPHX1 | NM_001136018.4 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
EPHX1 | ENST00000272167.10 | c.34G>A | p.Gly12Ser | missense_variant | 2/9 | 1 | NM_001136018.4 | ENSP00000272167 | P1 | |
EPHX1 | ENST00000366837.5 | c.34G>A | p.Gly12Ser | missense_variant | 2/9 | 1 | ENSP00000355802 | P1 | ||
EPHX1 | ENST00000614058.4 | c.34G>A | p.Gly12Ser | missense_variant | 2/9 | 1 | ENSP00000480004 | P1 | ||
EPHX1 | ENST00000448202.5 | c.34G>A | p.Gly12Ser | missense_variant | 2/4 | 2 | ENSP00000408469 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151690Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251352Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135842
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461670Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 727118
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GnomAD4 genome AF: 0.00000659 AC: 1AN: 151690Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74050
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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 | Oct 26, 2022 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.;T;T;.
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;M;.;M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;.;D
REVEL
Benign
Sift
Benign
T;T;D;.;T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.95
.;P;.;P;P
Vest4
0.22, 0.27, 0.21
MutPred
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
MPC
0.25
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at