Genetic Variant NM_001141.3:c.312C>G (chr17-8039550-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001141.3(ALOX15B):c.312C>G(p.Phe104Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,389,626 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ALOX15B
NM_001141.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.22

Publications

0 publications found

Variant links:

Genes affected

ALOX15B (HGNC:434): (arachidonate 15-lipoxygenase type B) This gene encodes a member of the lipoxygenase family of structurally related nonheme iron dioxygenases involved in the production of fatty acid hydroperoxides. The encoded protein converts arachidonic acid exclusively to 15S-hydroperoxyeicosatetraenoic acid, while metabolizing linoleic acid less effectively. This gene is located in a cluster of related genes and a pseudogene that spans approximately 100 kilobases on the short arm of chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ALOX15B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.936

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALOX15B	NM_001141.3	MANE Select	c.312C>G	p.Phe104Leu	missense	Exon 2 of 14	NP_001132.2	O15296-1
ALOX15B	NM_001039130.2		c.312C>G	p.Phe104Leu	missense	Exon 2 of 13	NP_001034219.1	O15296-4
ALOX15B	NM_001039131.2		c.312C>G	p.Phe104Leu	missense	Exon 2 of 12	NP_001034220.1	O15296-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALOX15B	ENST00000380183.9	TSL:1 MANE Select	c.312C>G	p.Phe104Leu	missense	Exon 2 of 14	ENSP00000369530.4	O15296-1
ALOX15B	ENST00000380173.6	TSL:1	c.312C>G	p.Phe104Leu	missense	Exon 2 of 13	ENSP00000369520.2	O15296-4
ALOX15B	ENST00000573359.1	TSL:1	c.312C>G	p.Phe104Leu	missense	Exon 2 of 12	ENSP00000460332.2	O15296-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.20e-7

AC:

AN:

1389626

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

686320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31670

American (AMR)

AF:

0.00

AC:

AN:

36162

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25168

East Asian (EAS)

AF:

0.00

AC:

AN:

35846

South Asian (SAS)

AF:

0.00

AC:

AN:

79792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37538

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5032

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1080482

Other (OTH)

AF:

0.0000173

AC:

AN:

57936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.69

M_CAP

Benign

0.039

MetaRNN

Pathogenic

0.94

MetaSVM

Uncertain

0.53

MutationAssessor

Pathogenic

3.7

PhyloP100

2.2

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-5.3

REVEL

Pathogenic

0.79

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.76

MutPred

0.87

Loss of sheet (P = 0.302)

MVP

0.96

MPC

0.19

ClinPred

1.0

GERP RS

4.2

PromoterAI

-0.039

Neutral

(source)

Varity_R

0.94

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over