GeneBe

rs41351946

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001629.4(ALOX5AP):​c.123C>G​(p.Ser41Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S41S) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Consequence

ALOX5AP
NM_001629.4 missense

Scores

1
8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.833

Publications

1 publications found
Variant links:
Genes affected
ALOX5AP (HGNC:436): (arachidonate 5-lipoxygenase activating protein) This gene encodes a protein which, with 5-lipoxygenase, is required for leukotriene synthesis. Leukotrienes are arachidonic acid metabolites which have been implicated in various types of inflammatory responses, including asthma, arthritis and psoriasis. This protein localizes to the plasma membrane. Inhibitors of its function impede translocation of 5-lipoxygenase from the cytoplasm to the cell membrane and inhibit 5-lipoxygenase activation. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Feb 2011]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALOX5APNM_001629.4 linkc.123C>G p.Ser41Arg missense_variant Exon 2 of 5 ENST00000380490.5 NP_001620.2 P20292
ALOX5APNM_001204406.2 linkc.294C>G p.Ser98Arg missense_variant Exon 3 of 6 NP_001191335.1 P20292A0A087WW23
ALOX5APXM_017020522.3 linkc.-118C>G 5_prime_UTR_variant Exon 1 of 5 XP_016876011.1
LOC124903146XR_007063743.1 linkn.220+397G>C intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALOX5APENST00000380490.5 linkc.123C>G p.Ser41Arg missense_variant Exon 2 of 5 1 NM_001629.4 ENSP00000369858.3 P20292
ALOX5APENST00000617770.4 linkc.294C>G p.Ser98Arg missense_variant Exon 3 of 6 1 ENSP00000479870.1 A0A087WW23
ALOX5APENST00000479597.1 linkn.263C>G non_coding_transcript_exon_variant Exon 2 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251420
AF XY:
0.00000736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.63
BayesDel_addAF
Benign
-0.0048
T
BayesDel_noAF
Uncertain
-0.080
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.031
T;T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.75
T;T
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.43
T;T
MetaSVM
Benign
-0.44
T
MutationAssessor
Benign
0.69
.;N
PhyloP100
0.83
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.1
.;N
REVEL
Uncertain
0.32
Sift
Uncertain
0.0040
.;D
Sift4G
Benign
0.16
T;T
Polyphen
1.0
.;D
Vest4
0.53
MutPred
0.53
.;Gain of catalytic residue at S41 (P = 0.0036);
MVP
0.62
MPC
0.69
ClinPred
0.70
D
GERP RS
5.7
Varity_R
0.81
gMVP
0.56
Mutation Taster
=82/18
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs41351946; hg19: chr13-31318249; API