Genetic Variant NM_000697.3:c.61C>T (chr17-6996178-C-T) – 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.61C>T(p.Arg21Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R21S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ALOX12
NM_000697.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.307

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=0.3947611).

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.61C>T	p.Arg21Cys	missense	Exon 1 of 14	NP_000688.2	P18054
	ALOX12-AS1	NR_040089.1		n.234-10638G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALOX12	ENST00000251535.11	TSL:1 MANE Select	c.61C>T	p.Arg21Cys	missense	Exon 1 of 14	ENSP00000251535.6	P18054
ALOX12	ENST00000915595.1		c.61C>T	p.Arg21Cys	missense	Exon 1 of 14	ENSP00000585654.1
MIR497HG	ENST00000399541.7	TSL:2	n.250-10638G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1101268

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

521714

African (AFR)

AF:

0.00

AC:

AN:

23008

American (AMR)

AF:

0.00

AC:

AN:

8438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14430

East Asian (EAS)

AF:

0.00

AC:

AN:

26674

South Asian (SAS)

AF:

0.00

AC:

AN:

21034

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35834

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3796

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

924038

Other (OTH)

AF:

0.00

AC:

AN:

44016

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.093

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.3

PhyloP100

-0.31

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.4

REVEL

Benign

0.21

Sift

Benign

0.14

Sift4G

Uncertain

0.053

Polyphen

0.97

Vest4

0.20

MutPred

0.69

Loss of MoRF binding (P = 0.004)

MVP

0.81

MPC

0.38

ClinPred

0.76

GERP RS

2.9

PromoterAI

0.097

Neutral

(source)

Varity_R

0.087

gMVP

0.68

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