17-8072899-TC-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_001139.3(ALOX12B):c.1977del(p.Arg660GlyfsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 frameshift
NM_001139.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.323
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 11 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-8072899-TC-T is Pathogenic according to our data. Variant chr17-8072899-TC-T is described in ClinVar as [Pathogenic]. Clinvar id is 995753.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| ALOX12B | NM_001139.3 | c.1977del | p.Arg660GlyfsTer3 | frameshift_variant | 15/15 | ENST00000647874.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ALOX12B | ENST00000647874.1 | c.1977del | p.Arg660GlyfsTer3 | frameshift_variant | 15/15 | NM_001139.3 | P1 | ||
| ALOX12B | ENST00000649809.1 | c.1041del | p.Arg348GlyfsTer3 | frameshift_variant | 8/8 | ||||
| ALOX12B | ENST00000650441.1 | n.400del | non_coding_transcript_exon_variant | 4/4 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250910Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135634
GnomAD3 exomes
AF:
AC:
1
AN:
250910
Hom.:
AF XY:
AC XY:
1
AN XY:
135634
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461806Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727194
GnomAD4 exome
AF:
AC:
4
AN:
1461806
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
727194
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
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:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at