Variant chr17-4632276-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000293761.8(ALOX15):c.1546C>T(p.Pro516Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ALOX15
ENST00000293761.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

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]

ALOX15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.759

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX15	NM_001140.5 linkuse as main transcript	c.1546C>T	p.Pro516Ser	missense_variant	12/14	ENST00000293761.8	NP_001131.3	P16050-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ALOX15	ENST00000293761.8 linkuse as main transcript	c.1546C>T	p.Pro516Ser	missense_variant	12/14	1	NM_001140.5	ENSP00000293761.3	P16050-1
ALOX15	ENST00000570836.6 linkuse as main transcript	c.1546C>T	p.Pro516Ser	missense_variant	13/15	2		ENSP00000458832.1	P16050-1
ALOX15	ENST00000574640.1 linkuse as main transcript	c.1429C>T	p.Pro477Ser	missense_variant	12/14	2		ENSP00000460483.1	P16050-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251328

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461730

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.1546C>T (p.P516S) alteration is located in exon 12 (coding exon 12) of the ALOX15 gene. This alteration results from a C to T substitution at nucleotide position 1546, causing the proline (P) at amino acid position 516 to be replaced by a serine (S). 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

0.45

BayesDel_addAF

Benign

-0.00096

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.87

D;D;.

Eigen

Uncertain

0.38

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.35

LIST_S2

Uncertain

0.87

.;D;D

M_CAP

Benign

0.012

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Uncertain

0.24

MutationAssessor

Pathogenic

3.1

M;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-6.7

.;D;.

REVEL

Uncertain

0.47

Sift

Uncertain

0.0040

.;D;.

Sift4G

Uncertain

0.010

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.49

MVP

0.88

MPC

0.50

ClinPred

0.98

GERP RS

3.1

Varity_R

0.37

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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