Variant chr19-15228023-T-G 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.694A>C(p.Lys232Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

EPHX3
NM_024794.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

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:

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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=0.2248022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EPHX3	NM_024794.3 linkuse as main transcript	c.694A>C	p.Lys232Gln	missense_variant	5/7	ENST00000221730.8
EPHX3	NM_001142886.2 linkuse as main transcript	c.694A>C	p.Lys232Gln	missense_variant	6/8
EPHX3	XM_024451725.2 linkuse as main transcript	c.694A>C	p.Lys232Gln	missense_variant	7/9
EPHX3	XM_047439452.1 linkuse as main transcript	c.694A>C	p.Lys232Gln	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
EPHX3	ENST00000221730.8 linkuse as main transcript	c.694A>C	p.Lys232Gln	missense_variant	5/7	1	NM_024794.3	P1
EPHX3	ENST00000435261.5 linkuse as main transcript	c.694A>C	p.Lys232Gln	missense_variant	6/8	1		P1
EPHX3	ENST00000602233.5 linkuse as main transcript	c.694A>C	p.Lys232Gln	missense_variant	7/9	5		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457928

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725320

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 20, 2023

The c.694A>C (p.K232Q) alteration is located in exon 5 (coding exon 5) of the EPHX3 gene. This alteration results from a A to C substitution at nucleotide position 694, causing the lysine (K) at amino acid position 232 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

0.12

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.028

T;T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.088

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.73

.;T;.

M_CAP

Benign

0.039

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.7

L;L;L

MutationTaster

Benign

0.71

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

N;N;.

REVEL

Benign

0.14

Sift

Benign

0.32

T;T;.

Sift4G

Benign

0.32

T;T;T

Polyphen

0.021

B;B;B

Vest4

0.45

MutPred

0.49

Loss of ubiquitination at K232 (P = 0.0446);Loss of ubiquitination at K232 (P = 0.0446);Loss of ubiquitination at K232 (P = 0.0446);

MVP

0.34

MPC

0.19

ClinPred

0.15

GERP RS

5.0

Varity_R

0.14

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over