Variant 19-15228089-G-A 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.628C>T(p.His210Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000338 in 1,478,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

EPHX3
NM_024794.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.33

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=0.15914068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EPHX3	NM_024794.3 linkuse as main transcript	c.628C>T	p.His210Tyr	missense_variant	5/7	ENST00000221730.8
EPHX3	NM_001142886.2 linkuse as main transcript	c.628C>T	p.His210Tyr	missense_variant	6/8
EPHX3	XM_024451725.2 linkuse as main transcript	c.628C>T	p.His210Tyr	missense_variant	7/9
EPHX3	XM_047439452.1 linkuse as main transcript	c.628C>T	p.His210Tyr	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
EPHX3	ENST00000221730.8 linkuse as main transcript	c.628C>T	p.His210Tyr	missense_variant	5/7	1	NM_024794.3	P1
EPHX3	ENST00000435261.5 linkuse as main transcript	c.628C>T	p.His210Tyr	missense_variant	6/8	1		P1
EPHX3	ENST00000602233.5 linkuse as main transcript	c.628C>T	p.His210Tyr	missense_variant	7/9	5		P1

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151304

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249542

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135110

show subpopulations

Gnomad AFR exome

AF:

0.0000619

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000301

AC:

AN:

1327362

Hom.:

Cov.:

AF XY:

0.00000301

AC XY:

AN XY:

664888

show subpopulations

Gnomad4 AFR exome

AF:

0.0000327

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:

0.00000300

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151304

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73870

show subpopulations

Gnomad4 AFR

AF:

0.0000243

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

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

Jun 07, 2024

The c.628C>T (p.H210Y) alteration is located in exon 5 (coding exon 5) of the EPHX3 gene. This alteration results from a C to T substitution at nucleotide position 628, causing the histidine (H) at amino acid position 210 to be replaced by a tyrosine (Y). 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

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.045

T;T;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.58

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.69

.;T;.

M_CAP

Benign

0.0079

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.7

L;L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.5

N;N;.

REVEL

Benign

0.13

Sift

Benign

0.045

D;D;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.37

MutPred

0.43

Loss of disorder (P = 0.0695);Loss of disorder (P = 0.0695);Loss of disorder (P = 0.0695);

MVP

0.085

MPC

0.20

ClinPred

0.091

GERP RS

3.6

Varity_R

0.091

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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.

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