Variant chr19-15228067-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024794.3(EPHX3):c.650G>A(p.Arg217His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,359,108 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R217C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

EPHX3
NM_024794.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.426

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]

EPHX3 links:

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=0.2024681).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EPHX3	NM_024794.3 linkuse as main transcript	c.650G>A	p.Arg217His	missense_variant	5/7	ENST00000221730.8
EPHX3	NM_001142886.2 linkuse as main transcript	c.650G>A	p.Arg217His	missense_variant	6/8
EPHX3	XM_024451725.2 linkuse as main transcript	c.650G>A	p.Arg217His	missense_variant	7/9
EPHX3	XM_047439452.1 linkuse as main transcript	c.650G>A	p.Arg217His	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
EPHX3	ENST00000221730.8 linkuse as main transcript	c.650G>A	p.Arg217His	missense_variant	5/7	1	NM_024794.3	P1
EPHX3	ENST00000435261.5 linkuse as main transcript	c.650G>A	p.Arg217His	missense_variant	6/8	1		P1
EPHX3	ENST00000602233.5 linkuse as main transcript	c.650G>A	p.Arg217His	missense_variant	7/9	5		P1

Frequencies

GnomAD3 genomes

AF:

0.000153

AC:

AN:

137290

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000147

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:

0.000234

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000132

AC:

AN:

250794

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000183

AC:

223

AN:

1221704

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

105

AN XY:

605396

show subpopulations

Gnomad4 AFR exome

AF:

0.000265

Gnomad4 AMR exome

AF:

0.0000266

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000132

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000204

Gnomad4 OTH exome

AF:

0.000202

GnomAD4 genome

AF:

0.000153

AC:

AN:

137404

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

66076

show subpopulations

Gnomad4 AFR

AF:

0.000107

Gnomad4 AMR

AF:

0.000147

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000234

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000239

Hom.:

Bravo

AF:

0.000166

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000652

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

Jan 09, 2024

The c.650G>A (p.R217H) alteration is located in exon 5 (coding exon 5) of the EPHX3 gene. This alteration results from a G to A substitution at nucleotide position 650, causing the arginine (R) at amino acid position 217 to be replaced by a histidine (H). 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

0.076

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T;T

Eigen

Benign

0.14

Eigen_PC

Benign

-0.0059

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.71

.;T;.

M_CAP

Benign

0.013

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;M

MutationTaster

Benign

0.90

D;D

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.4

D;D;.

REVEL

Benign

0.11

Sift

Benign

0.042

D;D;.

Sift4G

Uncertain

0.058

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.34

MVP

0.32

MPC

0.27

ClinPred

0.12

GERP RS

2.9

Varity_R

0.089

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: -26

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over