rs760078796

Variant summary

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

The NM_000698.5(ALOX5):ā€‹c.302A>Cā€‹(p.Tyr101Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,204 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: š‘“ 0.0000066 ( 0 hom., cov: 33)

Consequence

ALOX5
NM_000698.5 missense

Scores

5
10
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.84
Variant links:
Genes affected
ALOX5 (HGNC:435): (arachidonate 5-lipoxygenase) This gene encodes a member of the lipoxygenase gene family and plays a dual role in the synthesis of leukotrienes from arachidonic acid. The encoded protein, which is expressed specifically in bone marrow-derived cells, catalyzes the conversion of arachidonic acid to 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid, and further to the allylic epoxide 5(S)-trans-7,9-trans-11,14-cis-eicosatetrenoic acid (leukotriene A4). Leukotrienes are important mediators of a number of inflammatory and allergic conditions. Mutations in the promoter region of this gene lead to a diminished response to antileukotriene drugs used in the treatment of asthma and may also be associated with atherosclerosis and several cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

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, 0.877

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALOX5NM_000698.5 linkc.302A>C p.Tyr101Ser missense_variant Exon 2 of 14 ENST00000374391.7 NP_000689.1 P09917-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALOX5ENST00000374391.7 linkc.302A>C p.Tyr101Ser missense_variant Exon 2 of 14 1 NM_000698.5 ENSP00000363512.2 P09917-1
ALOX5ENST00000542434.5 linkc.302A>C p.Tyr101Ser missense_variant Exon 2 of 13 1 ENSP00000437634.1 P09917-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152204
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152204
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.79
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.54
.;D;T
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Uncertain
0.94
D
M_CAP
Benign
0.043
D
MetaRNN
Pathogenic
0.88
D;D;D
MetaSVM
Benign
-0.34
T
MutationAssessor
Uncertain
2.5
M;M;.
PrimateAI
Uncertain
0.65
T
PROVEAN
Pathogenic
-7.9
D;D;.
REVEL
Uncertain
0.40
Sift
Uncertain
0.0010
D;D;.
Sift4G
Uncertain
0.0040
D;D;D
Polyphen
1.0
.;D;.
Vest4
0.72
MutPred
0.80
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
0.87
MPC
1.2
ClinPred
1.0
D
GERP RS
5.1
Varity_R
0.95
gMVP
0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs760078796; hg19: chr10-45878082; API