Genetic Variant NM_021628.3:c.*24A>G (chr17-8096603-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_021628.3(ALOXE3):c.*24A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,074,220 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 13 hom. )

Consequence

ALOXE3
NM_021628.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0120

Publications

0 publications found

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 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

ALOXE3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-8096603-T-C is Benign according to our data. Variant chr17-8096603-T-C is described in ClinVar as Benign. ClinVar VariationId is 325954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00615 (936/152262) while in subpopulation AFR AF = 0.0217 (902/41560). AF 95% confidence interval is 0.0205. There are 11 homozygotes in GnomAd4. There are 434 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALOXE3	NM_021628.3	MANE Select	c.*24A>G	3_prime_UTR	Exon 16 of 16	NP_067641.2	Q9BYJ1-1
ALOXE3	NM_001165960.1		c.*24A>G	3_prime_UTR	Exon 16 of 16	NP_001159432.1	Q9BYJ1-2
ALOXE3	NM_001369446.1		c.*24A>G	3_prime_UTR	Exon 15 of 15	NP_001356375.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALOXE3	ENST00000448843.7	TSL:1 MANE Select	c.*24A>G	3_prime_UTR	Exon 16 of 16	ENSP00000400581.2	Q9BYJ1-1
ALOXE3	ENST00000380149.6	TSL:1	c.*24A>G	3_prime_UTR	Exon 15 of 15	ENSP00000369494.2	Q9BYJ1-1
ALOXE3	ENST00000318227.4	TSL:2	c.*24A>G	3_prime_UTR	Exon 16 of 16	ENSP00000314879.4	Q9BYJ1-1

Frequencies

GnomAD3 genomes

AF:

0.00607

AC:

924

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00167

AC:

420

AN:

251454

AF XY:

0.00121

show subpopulations

Gnomad AFR exome

AF:

0.0233

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000770

AC:

710

AN:

921958

Hom.:

Cov.:

AF XY:

0.000629

AC XY:

302

AN XY:

480424

show subpopulations

African (AFR)

AF:

0.0245

AC:

563

AN:

22978

American (AMR)

AF:

0.00109

AC:

AN:

44036

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22688

East Asian (EAS)

AF:

0.00

AC:

AN:

37256

South Asian (SAS)

AF:

0.000106

AC:

AN:

75566

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53226

Middle Eastern (MID)

AF:

0.000856

AC:

AN:

4674

European-Non Finnish (NFE)

AF:

0.00000646

AC:

AN:

619110

Other (OTH)

AF:

0.00196

AC:

AN:

42424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00615

AC:

936

AN:

152262

Hom.:

Cov.:

AF XY:

0.00583

AC XY:

434

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0217

AC:

902

AN:

41560

American (AMR)

AF:

0.00157

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68012

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

134

179

224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00272

Hom.:

Bravo

AF:

0.00721

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive congenital ichthyosis 3 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.4

(source)

DANN

Benign

0.80

PhyloP100

-0.012

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over