Genetic Variant ALOX12:p.His69Gln (chr17-6996897-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000697.3(ALOX12):c.207C>G(p.His69Gln) 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 1,461,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ALOX12
NM_000697.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.73

Publications

0 publications found

Variant links:

Genes affected

ALOX12 (HGNC:429): (arachidonate 12-lipoxygenase, 12S type) This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on different polyunsaturated fatty acid substrates to generate bioactive lipid mediators including eicosanoids and lipoxins. The encoded enzyme and its reaction products have been shown to regulate platelet function. Elevated expression of this gene has been observed in pancreatic islets derived from human diabetes patients. Allelic variants in this gene may be associated with susceptibility to toxoplasmosis. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]

ALOX12 links:

MIR497HG (HGNC:39523): (mir-497-195 cluster host gene)

MIR497HG links:

ALOX12-AS1 (HGNC:51342): (ALOX12 antisense RNA 1)

ALOX12-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32600284).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000697.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12	NM_000697.3	MANE Select	c.207C>G	p.His69Gln	missense	Exon 2 of 14	NP_000688.2	P18054
	ALOX12-AS1	NR_040089.1		n.234-11357G>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALOX12	ENST00000251535.11	TSL:1 MANE Select	c.207C>G	p.His69Gln	missense	Exon 2 of 14	ENSP00000251535.6	P18054
ALOX12	ENST00000915595.1		c.207C>G	p.His69Gln	missense	Exon 2 of 14	ENSP00000585654.1
MIR497HG	ENST00000399541.7	TSL:2	n.250-11357G>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111868

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.14

Eigen

Benign

0.071

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.71

M_CAP

Benign

0.051

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.7

PhyloP100

1.7

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.82

REVEL

Benign

0.11

Sift

Benign

0.17

Sift4G

Uncertain

0.056

Polyphen

0.70

Vest4

0.39

MutPred

0.57

Gain of catalytic residue at H69 (P = 0.0283)

MVP

0.75

MPC

0.29

ClinPred

0.37

GERP RS

3.8

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.10

gMVP

0.39

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over