chr17-6996865-CTC-ATA

Variant names:

• chr17-6996865-CTC-ATA
• NM_000697.3:c.175_177delCTCinsATA
• ALOX12 p.Leu59Ile

Variant summary

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

The NM_000697.3(ALOX12):​c.175_177delCTCinsATA​(p.Leu59Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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)
• Consequence: ALOX12 NM_000697.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989
• Publications: 0 publications found

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]

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

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.175_177delCTCinsATA	p.Leu59Ile	missense	N/A	NP_000688.2	P18054
	ALOX12-AS1	NR_040089.1		n.234-11327_234-11325delGAGinsTAT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12	ENST00000251535.11	TSL:1 MANE Select	c.175_177delCTCinsATA	p.Leu59Ile	missense	N/A	ENSP00000251535.6	P18054
	ALOX12	ENST00000915595.1		c.175_177delCTCinsATA	p.Leu59Ile	missense	N/A	ENSP00000585654.1
	MIR497HG	ENST00000399541.7	TSL:2	n.250-11327_250-11325delGAGinsTAT		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.99

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-6900184;