17-4632863-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001140.5(ALOX15):​c.1538G>A​(p.Arg513Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

ALOX15
NM_001140.5 missense, splice_region

Scores

1
18
Splicing: ADA: 0.00003990
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0440
Variant links:
Genes affected
ALOX15 (HGNC:433): (arachidonate 15-lipoxygenase) This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on various polyunsaturated fatty acid substrates to generate various bioactive lipid mediators such as eicosanoids, hepoxilins, lipoxins, and other molecules. The encoded enzyme and its reaction products have been shown to regulate inflammation and immunity. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07620597).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALOX15NM_001140.5 linkc.1538G>A p.Arg513Gln missense_variant, splice_region_variant Exon 11 of 14 ENST00000293761.8 NP_001131.3 P16050-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALOX15ENST00000293761.8 linkc.1538G>A p.Arg513Gln missense_variant, splice_region_variant Exon 11 of 14 1 NM_001140.5 ENSP00000293761.3 P16050-1
ALOX15ENST00000570836.6 linkc.1538G>A p.Arg513Gln missense_variant, splice_region_variant Exon 12 of 15 2 ENSP00000458832.1 P16050-1
ALOX15ENST00000574640.1 linkc.1421G>A p.Arg474Gln missense_variant, splice_region_variant Exon 11 of 14 2 ENSP00000460483.1 P16050-2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251224
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135800
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000868
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:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461842
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1538G>A (p.R513Q) alteration is located in exon 11 (coding exon 11) of the ALOX15 gene. This alteration results from a G to A substitution at nucleotide position 1538, causing the arginine (R) at amino acid position 513 to be replaced by a glutamine (Q). 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
Benign
0.078
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
10
DANN
Benign
0.95
DEOGEN2
Benign
0.27
T;T;.
Eigen
Benign
-0.87
Eigen_PC
Benign
-0.90
FATHMM_MKL
Benign
0.045
N
LIST_S2
Uncertain
0.89
.;D;D
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.076
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.99
L;L;.
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-1.3
.;N;.
REVEL
Benign
0.085
Sift
Benign
0.16
.;T;.
Sift4G
Benign
0.19
T;T;T
Polyphen
0.13
B;B;.
Vest4
0.048
MVP
0.59
MPC
0.21
ClinPred
0.049
T
GERP RS
-0.91
Varity_R
0.12
gMVP
0.11

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000040
dbscSNV1_RF
Benign
0.0
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

LitVar

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

Other links and lift over

dbSNP: rs771288255; hg19: chr17-4536158; API