chr19-15227559-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024794.3(EPHX3):​c.961C>T​(p.Arg321Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,461,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

EPHX3
NM_024794.3 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.311723).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EPHX3NM_024794.3 linkuse as main transcriptc.961C>T p.Arg321Cys missense_variant 7/7 ENST00000221730.8
EPHX3NM_001142886.2 linkuse as main transcriptc.961C>T p.Arg321Cys missense_variant 8/8
EPHX3XM_024451725.2 linkuse as main transcriptc.961C>T p.Arg321Cys missense_variant 9/9
EPHX3XM_047439452.1 linkuse as main transcriptc.961C>T p.Arg321Cys missense_variant 9/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EPHX3ENST00000221730.8 linkuse as main transcriptc.961C>T p.Arg321Cys missense_variant 7/71 NM_024794.3 P1
EPHX3ENST00000435261.5 linkuse as main transcriptc.961C>T p.Arg321Cys missense_variant 8/81 P1
EPHX3ENST00000602233.5 linkuse as main transcriptc.961C>T p.Arg321Cys missense_variant 9/95 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250638
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135688
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:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000198
AC:
29
AN:
1461680
Hom.:
0
Cov.:
31
AF XY:
0.0000234
AC XY:
17
AN XY:
727150
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000234
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000567
Hom.:
0
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
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 GeneticsApr 25, 2024The c.961C>T (p.R321C) alteration is located in exon 7 (coding exon 7) of the EPHX3 gene. This alteration results from a C to T substitution at nucleotide position 961, causing the arginine (R) at amino acid position 321 to be replaced by a cysteine (C). 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
0.13
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T;T;T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Benign
0.50
D
LIST_S2
Benign
0.75
.;T;.
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.31
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.9
M;M;M
MutationTaster
Benign
0.99
N;N
PrimateAI
Benign
0.37
T
PROVEAN
Uncertain
-2.9
D;D;.
REVEL
Benign
0.10
Sift
Benign
0.11
T;T;.
Sift4G
Uncertain
0.055
T;T;T
Polyphen
1.0
D;D;D
Vest4
0.19
MVP
0.27
MPC
0.67
ClinPred
0.94
D
GERP RS
3.6
Varity_R
0.084
gMVP
0.51

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: rs3746204; hg19: chr19-15338370; API