Variant 17-8072905-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate

The NM_001139.3(ALOX12B):c.1972C>T(p.Pro658Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ALOX12B
NM_001139.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.61

Variant links:

Genes affected

ALOX12B (HGNC:430): (arachidonate 12-lipoxygenase, 12R type) This gene encodes an enzyme involved in the conversion of arachidonic acid to 12R-hydroxyeicosatetraenoic acid. Mutations in this gene are associated with nonbullous congenital ichthyosiform erythroderma. [provided by RefSeq, Sep 2015]

ALOX12B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.8

PP5

Variant 17-8072905-G-A is Pathogenic according to our data. Variant chr17-8072905-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3617005.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX12B	NM_001139.3 link	c.1972C>T	p.Pro658Ser	missense_variant	15/15	ENST00000647874.1	NP_001130.1	O75342

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX12B	ENST00000647874.1 link	c.1972C>T	p.Pro658Ser	missense_variant	15/15	NM_001139.3	ENSP00000497784.1	O75342
ALOX12B	ENST00000649809.1 link	c.1036C>T	p.Pro346Ser	missense_variant	8/8		ENSP00000496845.1	A0A3B3IRK2
ALOX12B	ENST00000650441.1 link	n.395C>T		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461740

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Uncertain

0.082

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.76

D;D;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

.;D;D

M_CAP

Uncertain

0.24

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Pathogenic

0.83

MutationAssessor

Uncertain

2.5

M;M;.

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-7.7

D;.;.

REVEL

Uncertain

0.50

Sift

Uncertain

0.019

D;.;.

Sift4G

Uncertain

0.046

D;.;.

Polyphen

0.98

D;D;.

Vest4

0.26

MutPred

0.57

Gain of phosphorylation at P658 (P = 0.0227);Gain of phosphorylation at P658 (P = 0.0227);.;

MVP

0.93

MPC

1.5

ClinPred

1.0

GERP RS

4.9

Varity_R

0.66

gMVP

0.88

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over