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GeneBe

19-15231003-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024794.3(EPHX3):​c.575G>A​(p.Arg192Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000967 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000098 ( 0 hom. )

Consequence

EPHX3
NM_024794.3 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81
Variant links:
Genes affected
EPHX3 (HGNC:23760): (epoxide hydrolase 3) Enables epoxide hydrolase activity. Involved in epoxide metabolic process. Located in intracellular membrane-bounded organelle and membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1785383).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EPHX3NM_024794.3 linkuse as main transcriptc.575G>A p.Arg192Gln missense_variant 4/7 ENST00000221730.8
EPHX3NM_001142886.2 linkuse as main transcriptc.575G>A p.Arg192Gln missense_variant 5/8
EPHX3XM_024451725.2 linkuse as main transcriptc.575G>A p.Arg192Gln missense_variant 6/9
EPHX3XM_047439452.1 linkuse as main transcriptc.575G>A p.Arg192Gln missense_variant 6/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EPHX3ENST00000221730.8 linkuse as main transcriptc.575G>A p.Arg192Gln missense_variant 4/71 NM_024794.3 P1
EPHX3ENST00000435261.5 linkuse as main transcriptc.575G>A p.Arg192Gln missense_variant 5/81 P1
EPHX3ENST00000602233.5 linkuse as main transcriptc.575G>A p.Arg192Gln missense_variant 6/95 P1

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152142
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000756
AC:
19
AN:
251316
Hom.:
0
AF XY:
0.0000663
AC XY:
9
AN XY:
135846
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000968
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000978
AC:
143
AN:
1461788
Hom.:
0
Cov.:
32
AF XY:
0.0000963
AC XY:
70
AN XY:
727188
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.000119
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152260
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.0000963
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000921
Hom.:
0
Bravo
AF:
0.000132
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000988
AC:
12
EpiCase
AF:
0.000218
EpiControl
AF:
0.000119

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 GeneticsAug 13, 2021The c.575G>A (p.R192Q) alteration is located in exon 4 (coding exon 4) of the EPHX3 gene. This alteration results from a G to A substitution at nucleotide position 575, causing the arginine (R) at amino acid position 192 to be replaced by a glutamine (Q). 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
0.11
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.078
T;T;T
Eigen
Uncertain
0.19
Eigen_PC
Benign
0.22
FATHMM_MKL
Benign
0.48
N
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-0.64
T
MutationAssessor
Benign
1.8
L;L;L
MutationTaster
Benign
0.65
N;N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.4
N;N;.
REVEL
Benign
0.12
Sift
Benign
0.079
T;T;.
Sift4G
Benign
0.13
T;T;T
Polyphen
0.77
P;P;P
Vest4
0.50
MVP
0.56
MPC
0.29
ClinPred
0.052
T
GERP RS
3.3
Varity_R
0.13
gMVP
0.48

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: rs139340007; hg19: chr19-15341814; COSMIC: COSV55656835; COSMIC: COSV55656835; API