chr19-15231263-T-C

Position:

• chr19-15231263-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024794.3(EPHX3):​c.463A>G​(p.Ile155Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: EPHX3 NM_024794.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.249

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]

ACMG classification

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=0.19566602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX3	NM_024794.3	c.463A>G	p.Ile155Val	missense_variant	3/7	ENST00000221730.8
EPHX3	NM_001142886.2	c.463A>G	p.Ile155Val	missense_variant	4/8
EPHX3	XM_024451725.2	c.463A>G	p.Ile155Val	missense_variant	5/9
EPHX3	XM_047439452.1	c.463A>G	p.Ile155Val	missense_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX3	ENST00000221730.8	c.463A>G	p.Ile155Val	missense_variant	3/7	1	NM_024794.3	P1
EPHX3	ENST00000435261.5	c.463A>G	p.Ile155Val	missense_variant	4/8	1		P1
EPHX3	ENST00000602233.5	c.463A>G	p.Ile155Val	missense_variant	5/9	5		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.463A>G (p.I155V) alteration is located in exon 3 (coding exon 3) of the EPHX3 gene. This alteration results from a A to G substitution at nucleotide position 463, causing the isoleucine (I) at amino acid position 155 to be replaced by a valine (V). 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	0.084
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.1
DANN	Benign	0.96
DEOGEN2	Benign	0.038	T;T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.61	.;T;.
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.36	N;N;N
MutationTaster	Benign	0.98	D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.35	N;N;.
REVEL	Benign	0.063
Sift	Benign	0.26	T;T;.
Sift4G	Benign	0.67	T;T;T
Polyphen		0.30	B;B;B
Vest4		0.31
MutPred		0.61		Loss of catalytic residue at L160 (P = 0.0646);Loss of catalytic residue at L160 (P = 0.0646);Loss of catalytic residue at L160 (P = 0.0646);
MVP		0.53
MPC		0.15
ClinPred		0.57	D
GERP RS		3.2
Varity_R		0.055
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-15342074;