17-8072914-C-T

Position:

• chr17-8072914-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_001139.3(ALOX12B):​c.1963G>A​(p.Glu655Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ALOX12B NM_001139.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.66

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]

ACMG classification

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, 0.857
• PP5: Variant 17-8072914-C-T is Pathogenic according to our data. Variant chr17-8072914-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 995717.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	c.1963G>A	p.Glu655Lys	missense_variant	15/15	ENST00000647874.1	NP_001130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX12B	ENST00000647874.1	c.1963G>A	p.Glu655Lys	missense_variant	15/15		NM_001139.3	ENSP00000497784	P1
ALOX12B	ENST00000649809.1	c.1027G>A	p.Glu343Lys	missense_variant	8/8			ENSP00000496845
ALOX12B	ENST00000650441.1	n.386G>A		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal recessive congenital ichthyosis 2 Pathogenic:1

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	0.84
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.75	D;D;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.97	.;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Pathogenic	0.98	D
MutationAssessor	Pathogenic	3.0	M;M;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.9	D;.;.
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0020	D;.;.
Sift4G	Uncertain	0.0020	D;.;.
Polyphen		0.99	D;D;.
Vest4		0.58
MutPred		0.66		Gain of methylation at E655 (P = 0.0072);Gain of methylation at E655 (P = 0.0072);.;
MVP		0.93
MPC		0.96
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.91
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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

Other links and lift over

dbSNP: rs1977010880; hg19: chr17-7976232;