Genetic Variant ALOX12:p.Thr364Thr (chr17-7001742-T-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000697.3(ALOX12):c.1092T>G(p.Thr364Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,613,744 control chromosomes in the GnomAD database, including 271,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26225 hom., cov: 31)

Exomes 𝑓: 0.58 ( 244896 hom. )

Consequence

ALOX12
NM_000697.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.75

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:

ALOX12-AS1 (HGNC:):

ALOX12-AS1 links:

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

ALOX12-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 17-7001742-T-G is Benign according to our data. Variant chr17-7001742-T-G is described in ClinVar as [Benign]. Clinvar id is 1247877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.75 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12	NM_000697.3 link	c.1092T>G	p.Thr364Thr	synonymous_variant	Exon 8 of 14	ENST00000251535.11	NP_000688.2	P18054
ALOX12	XM_011523780.3 link	c.885T>G	p.Thr295Thr	synonymous_variant	Exon 7 of 13		XP_011522082.2
ALOX12-AS1	NR_040089.1 link	n.233+8054A>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11 link	c.1092T>G	p.Thr364Thr	synonymous_variant	Exon 8 of 14	1	NM_000697.3	ENSP00000251535.6		P18054

Frequencies

GnomAD3 genomes

AF:

0.585

AC:

88894

AN:

151862

Hom.:

26193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.566

Gnomad AMI

AF:

0.600

Gnomad AMR

AF:

0.655

Gnomad ASJ

AF:

0.531

Gnomad EAS

AF:

0.527

Gnomad SAS

AF:

0.540

Gnomad FIN

AF:

0.657

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.581

Gnomad OTH

AF:

0.579

GnomAD3 exomes

AF:

0.592

AC:

148784

AN:

251418

Hom.:

44521

AF XY:

0.586

AC XY:

79675

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.568

Gnomad AMR exome

AF:

0.694

Gnomad ASJ exome

AF:

0.536

Gnomad EAS exome

AF:

0.511

Gnomad SAS exome

AF:

0.546

Gnomad FIN exome

AF:

0.670

Gnomad NFE exome

AF:

0.580

Gnomad OTH exome

AF:

0.581

GnomAD4 exome

AF:

0.578

AC:

844203

AN:

1461764

Hom.:

244896

Cov.:

AF XY:

0.576

AC XY:

419157

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.557

Gnomad4 AMR exome

AF:

0.689

Gnomad4 ASJ exome

AF:

0.533

Gnomad4 EAS exome

AF:

0.570

Gnomad4 SAS exome

AF:

0.547

Gnomad4 FIN exome

AF:

0.664

Gnomad4 NFE exome

AF:

0.574

Gnomad4 OTH exome

AF:

0.562

GnomAD4 genome

AF:

0.585

AC:

88975

AN:

151980

Hom.:

26225

Cov.:

AF XY:

0.590

AC XY:

43798

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.567

Gnomad4 AMR

AF:

0.655

Gnomad4 ASJ

AF:

0.531

Gnomad4 EAS

AF:

0.527

Gnomad4 SAS

AF:

0.540

Gnomad4 FIN

AF:

0.657

Gnomad4 NFE

AF:

0.581

Gnomad4 OTH

AF:

0.579

Alfa

AF:

0.576

Hom.:

30968

Bravo

AF:

0.583

Asia WGS

AF:

0.533

AC:

1857

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.52

DANN

Benign

0.30

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

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