Variant 19-15227850-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024794.3(EPHX3):c.778G>A(p.Glu260Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,613,900 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 1 hom. )

Consequence

EPHX3
NM_024794.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EPHX3	NM_024794.3 linkuse as main transcript	c.778G>A	p.Glu260Lys	missense_variant	6/7	ENST00000221730.8
EPHX3	NM_001142886.2 linkuse as main transcript	c.778G>A	p.Glu260Lys	missense_variant	7/8
EPHX3	XM_024451725.2 linkuse as main transcript	c.778G>A	p.Glu260Lys	missense_variant	8/9
EPHX3	XM_047439452.1 linkuse as main transcript	c.778G>A	p.Glu260Lys	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
EPHX3	ENST00000221730.8 linkuse as main transcript	c.778G>A	p.Glu260Lys	missense_variant	6/7	1	NM_024794.3	P1
EPHX3	ENST00000435261.5 linkuse as main transcript	c.778G>A	p.Glu260Lys	missense_variant	7/8	1		P1
EPHX3	ENST00000602233.5 linkuse as main transcript	c.778G>A	p.Glu260Lys	missense_variant	8/9	5		P1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.0000398

AC:

AN:

251274

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000231

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000246

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000656

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:

0.0000189

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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 29, 2021

The c.778G>A (p.E260K) alteration is located in exon 6 (coding exon 6) of the EPHX3 gene. This alteration results from a G to A substitution at nucleotide position 778, causing the glutamic acid (E) at amino acid position 260 to be replaced by a lysine (K). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;T;T

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

.;D;.

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.45

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

M;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.0

D;D;.

REVEL

Benign

0.18

Sift

Uncertain

0.029

D;D;.

Sift4G

Uncertain

0.032

D;D;D

Polyphen

0.97

D;D;D

Vest4

0.47

MutPred

0.66

Gain of ubiquitination at E260 (P = 0.0369);Gain of ubiquitination at E260 (P = 0.0369);Gain of ubiquitination at E260 (P = 0.0369);

MVP

0.24

MPC

0.22

ClinPred

0.76

GERP RS

4.3

Varity_R

0.21

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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