Variant rs137853024 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5

The NM_001139.3(ALOX12B):c.1734C>A(p.His578Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,836 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 Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ALOX12B
NM_001139.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: -0.926

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity LX12B_HUMAN

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.987

PP5

Variant 17-8073678-G-T is Pathogenic according to our data. Variant chr17-8073678-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 6084.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX12B	NM_001139.3 linkuse as main transcript	c.1734C>A	p.His578Gln	missense_variant	13/15	ENST00000647874.1	NP_001130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ALOX12B	ENST00000647874.1 linkuse as main transcript	c.1734C>A	p.His578Gln	missense_variant	13/15		NM_001139.3	ENSP00000497784	P1
ALOX12B	ENST00000649809.1 linkuse as main transcript	c.798C>A	p.His266Gln	missense_variant	6/8			ENSP00000496845
ALOX12B	ENST00000650441.1 linkuse as main transcript	n.157C>A		non_coding_transcript_exon_variant	2/4
ALOX12B	ENST00000577351.5 linkuse as main transcript	n.480-360C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251390

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Autosomal recessive congenital ichthyosis 2

Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Jan 01, 2002	- -
Pathogenic, no assertion criteria provided	clinical testing	Institute for Human Genetics, University Medical Center Freiburg	Jan 07, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.47

BayesDel_noAF

Pathogenic

0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.93

D;D;.

Eigen

Benign

0.056

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.31

LIST_S2

Uncertain

0.97

.;D;D

M_CAP

Pathogenic

0.81

MetaRNN

Pathogenic

0.99

D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.7

H;H;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-8.0

D;.;.

REVEL

Pathogenic

0.89

Sift

Pathogenic

0.0

D;.;.

Sift4G

Uncertain

0.0020

D;.;.

Polyphen

1.0

D;D;.

Vest4

0.97

MutPred

0.98

Gain of methylation at K577 (P = 0.1287);Gain of methylation at K577 (P = 0.1287);.;

MVP

0.91

MPC

1.4

ClinPred

1.0

GERP RS

-1.1

Varity_R

0.97

gMVP

0.94

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