1-92063132-T-G

Position:

• chr1-92063132-T-G

Variant summary

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

The NM_173567.5(EPHX4):​c.935T>G​(p.Val312Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EPHX4 NM_173567.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30

Genes affected

EPHX4 (HGNC:23758): (epoxide hydrolase 4) Predicted to enable hydrolase activity. Predicted to be integral component of 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=0.07966933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHX4	NM_173567.5	c.935T>G	p.Val312Gly	missense_variant	7/7	ENST00000370383.5	NP_775838.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHX4	ENST00000370383.5	c.935T>G	p.Val312Gly	missense_variant	7/7	1	NM_173567.5	ENSP00000359410.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461842 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727216

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Dec 06, 2024

The c.935T>G (p.V312G) alteration is located in exon 7 (coding exon 7) of the EPHX4 gene. This alteration results from a T to G substitution at nucleotide position 935, causing the valine (V) at amino acid position 312 to be replaced by a glycine (G). 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	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.85	L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.14
Sift	Benign	0.39	T
Sift4G	Benign	0.38	T
Polyphen		0.080	B
Vest4		0.30
MutPred		0.56		Gain of disorder (P = 0.017);
MVP		0.23
MPC		0.53
ClinPred		0.23	T
GERP RS		2.3
Varity_R		0.11
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-92528689;