chr17-8096146-C-T

Variant names:

• chr17-8096146-C-T
• rs1978528529
• NM_021628.3:c.*481G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021628.3(ALOXE3):​c.*481G>A variant causes a 3 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ALOXE3 NM_021628.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.375
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive congenital ichthyosis 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• congenital non-bullous ichthyosiform erythroderma

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• self-healing collodion baby

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021628.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOXE3	NM_021628.3	MANE Select	c.*481G>A		3_prime_UTR	Exon 16 of 16	NP_067641.2	Q9BYJ1-1
	ALOXE3	NM_001165960.1		c.*481G>A		3_prime_UTR	Exon 16 of 16	NP_001159432.1	Q9BYJ1-2
	ALOXE3	NM_001369446.1		c.*481G>A		3_prime_UTR	Exon 15 of 15	NP_001356375.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOXE3	ENST00000448843.7	TSL:1 MANE Select	c.*481G>A		3_prime_UTR	Exon 16 of 16	ENSP00000400581.2	Q9BYJ1-1
	ALOXE3	ENST00000380149.6	TSL:1	c.*481G>A		3_prime_UTR	Exon 15 of 15	ENSP00000369494.2	Q9BYJ1-1
	ALOXE3	ENST00000714145.1		c.*481G>A		3_prime_UTR	Exon 14 of 14	ENSP00000519434.1	A0AAQ5BHK9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 17934 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 9182

African (AFR) AF: 0.00 AC: 0 AN: 332

American (AMR) AF: 0.00 AC: 0 AN: 2622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 210

East Asian (EAS) AF: 0.00 AC: 0 AN: 1006

South Asian (SAS) AF: 0.00 AC: 0 AN: 2116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 34

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10224

Other (OTH) AF: 0.00 AC: 0 AN: 880

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Autosomal recessive congenital ichthyosis 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.49
DANN	Benign	0.26
PhyloP100		-0.38

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

Other links and lift over

dbSNP: rs1978528529; hg19: chr17-7999464;