17-4631688-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001140.5(ALOX15):​c.1901A>G​(p.Asp634Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ALOX15
NM_001140.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.02
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29902497).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALOX15NM_001140.5 linkc.1901A>G p.Asp634Gly missense_variant Exon 14 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.1901A>G p.Asp634Gly missense_variant Exon 14 of 14 1 NM_001140.5 ENSP00000293761.3 P16050-1
ALOX15ENST00000570836.6 linkc.1901A>G p.Asp634Gly missense_variant Exon 15 of 15 2 ENSP00000458832.1 P16050-1
ALOX15ENST00000574640.1 linkc.1784A>G p.Asp595Gly missense_variant Exon 14 of 14 2 ENSP00000460483.1 P16050-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 06, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1901A>G (p.D634G) alteration is located in exon 14 (coding exon 14) of the ALOX15 gene. This alteration results from a A to G substitution at nucleotide position 1901, causing the aspartic acid (D) at amino acid position 634 to be replaced by a glycine (G). 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
0.18
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.63
D;D;.
Eigen
Benign
0.17
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.80
.;T;T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.30
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;L;.
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-2.8
.;D;.
REVEL
Benign
0.16
Sift
Benign
0.098
.;T;.
Sift4G
Uncertain
0.049
D;D;D
Polyphen
0.94
P;P;.
Vest4
0.25
MVP
0.43
MPC
0.80
ClinPred
0.96
D
GERP RS
4.0
Varity_R
0.31
gMVP
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-4534983; API