Variant chr17-8096638-C-T 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_021628.3(ALOXE3):c.2125G>A(p.Val709Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000813 in 1,230,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)

Exomes 𝑓: 0.0000081 ( 0 hom. )

Consequence

ALOXE3
NM_021628.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43

Variant links:

Genes affected

ALOXE3 (HGNC:13743): (arachidonate lipoxygenase 3) This gene is a member of the lipoxygenase family, which are catabolized by arachidonic acid-derived compounds. The encoded enzyme is a hydroperoxide isomerase that synthesizes a unique type of epoxy alcohol (8R-hydroxy-11R,12R-epoxyeicosa-5Z,9E,14Z-trienoic acid) from 12R-hydroperoxyeicosatetraenoic acid (12R-HPETE). This epoxy alcohol can activate the the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha), which is implicated in epidermal differentiation. Loss of function of the enzyme encoded by this gene results in ichthyosis, implicating the function of this gene in the differentiation of human skin. This gene is part of a cluster of lipoxygenase genes on 17p13.1. Mutations in this gene result in nonbullous congenital ichthyosiform erythroderma (NCIE). Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

ALOXE3 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=0.18668011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ALOXE3	NM_021628.3 linkuse as main transcript	c.2125G>A	p.Val709Ile	missense_variant	16/16	ENST00000448843.7	NP_067641.2
ALOXE3	NM_001165960.1 linkuse as main transcript	c.2521G>A	p.Val841Ile	missense_variant	16/16		NP_001159432.1
ALOXE3	NM_001369446.1 linkuse as main transcript	c.2122G>A	p.Val708Ile	missense_variant	15/15		NP_001356375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOXE3	ENST00000448843.7 linkuse as main transcript	c.2125G>A	p.Val709Ile	missense_variant	16/16	1	NM_021628.3	ENSP00000400581	P1	Q9BYJ1-1
ALOXE3	ENST00000380149.6 linkuse as main transcript	c.2125G>A	p.Val709Ile	missense_variant	15/15	1		ENSP00000369494	P1	Q9BYJ1-1
ALOXE3	ENST00000318227.4 linkuse as main transcript	c.2125G>A	p.Val709Ile	missense_variant	16/16	2		ENSP00000314879	P1	Q9BYJ1-1
ALOXE3	ENST00000583808.1 linkuse as main transcript	n.362G>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000813

AC:

AN:

1230608

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

623264

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000405

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000777

Gnomad4 OTH exome

AF:

0.0000190

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.2125G>A (p.V709I) alteration is located in exon 16 (coding exon 15) of the ALOXE3 gene. This alteration results from a G to A substitution at nucleotide position 2125, causing the valine (V) at amino acid position 709 to be replaced by an isoleucine (I). 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

Uncertain

0.041

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.066

.;T;.

Eigen

Benign

0.0038

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.051

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

0.72

.;N;.

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.45

N;N;N

REVEL

Benign

0.27

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.41

T;T;T

Polyphen

0.93

.;P;.

Vest4

0.16

MutPred

0.48

.;Gain of glycosylation at S708 (P = 0.0929);.;

MVP

0.74

MPC

0.11

ClinPred

0.71

GERP RS

4.4

Varity_R

0.066

gMVP

0.52

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

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