17-8044867-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001141.3(ALOX15B):c.715G>A(p.Ala239Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,611,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ALOX15B
NM_001141.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

Variant links:

Genes affected

ALOX15B (HGNC:434): (arachidonate 15-lipoxygenase type B) This gene encodes a member of the lipoxygenase family of structurally related nonheme iron dioxygenases involved in the production of fatty acid hydroperoxides. The encoded protein converts arachidonic acid exclusively to 15S-hydroperoxyeicosatetraenoic acid, while metabolizing linoleic acid less effectively. This gene is located in a cluster of related genes and a pseudogene that spans approximately 100 kilobases on the short arm of chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ALOX15B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.887

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX15B	NM_001141.3 link	c.715G>A	p.Ala239Thr	missense_variant	Exon 6 of 14	ENST00000380183.9	NP_001132.2	O15296-1
ALOX15B	NM_001039130.2 link	c.715G>A	p.Ala239Thr	missense_variant	Exon 6 of 13		NP_001034219.1	O15296-4
ALOX15B	NM_001039131.2 link	c.715G>A	p.Ala239Thr	missense_variant	Exon 6 of 12		NP_001034220.1	O15296-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX15B	ENST00000380183.9 link	c.715G>A	p.Ala239Thr	missense_variant	Exon 6 of 14	1	NM_001141.3	ENSP00000369530.4		O15296-1

Frequencies

GnomAD3 genomes

AF:

0.0000734

AC:

AN:

149794

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251180

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461716

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000734

AC:

AN:

149794

Hom.:

Cov.:

AF XY:

0.0000686

AC XY:

AN XY:

72844

show subpopulations

Gnomad4 AFR

AF:

0.000247

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.715G>A (p.A239T) alteration is located in exon 6 (coding exon 6) of the ALOX15B gene. This alteration results from a G to A substitution at nucleotide position 715, causing the alanine (A) at amino acid position 239 to be replaced by a threonine (T). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.42

T;D;.;.

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Pathogenic

0.33

MetaRNN

Pathogenic

0.89

D;D;D;D

MetaSVM

Uncertain

0.59

MutationAssessor

Pathogenic

3.0

M;.;M;M

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.3

N;.;N;.

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0020

D;.;D;.

Sift4G

Uncertain

0.025

D;D;D;D

Polyphen

0.43

B;.;B;P

Vest4

0.35

MutPred

0.90

Loss of catalytic residue at A239 (P = 0.0603);Loss of catalytic residue at A239 (P = 0.0603);Loss of catalytic residue at A239 (P = 0.0603);Loss of catalytic residue at A239 (P = 0.0603);

MVP

0.94

MPC

0.62

ClinPred

0.88

GERP RS

3.3

Varity_R

0.71

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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