Genetic Variant NM_000697.3:c.1452A>C (chr17-7006519-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000697.3(ALOX12):c.1452A>C(p.Gln484His) 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 1,461,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q484Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ALOX12
NM_000697.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.756

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12	NM_000697.3 link	c.1452A>C	p.Gln484His	missense_variant	Exon 11 of 14	ENST00000251535.11	NP_000688.2	P18054
ALOX12	XM_011523780.3 link	c.1245A>C	p.Gln415His	missense_variant	Exon 10 of 13		XP_011522082.2
ALOX12-AS1	NR_040089.1 link	n.233+3277T>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11 link	c.1452A>C	p.Gln484His	missense_variant	Exon 11 of 14	1	NM_000697.3	ENSP00000251535.6		P18054

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461564

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111880

Other (OTH)

AF:

0.00

AC:

AN:

60378

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

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.15

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.13

M_CAP

Benign

0.0017

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.49

PhyloP100

-0.76

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

REVEL

Benign

0.018

Sift

Benign

0.18

Sift4G

Benign

0.30

Polyphen

0.0010

Vest4

0.087

MutPred

0.47

Loss of stability (P = 0.0631);

MVP

0.37

MPC

0.26

ClinPred

0.13

GERP RS

-3.3

Varity_R

0.17

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.27

Position offset: 3

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over