rs397514527
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001139.3(ALOX12B):c.1294C>T(p.Arg432Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 1,398,326 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 (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001139.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALOX12B | NM_001139.3 | c.1294C>T | p.Arg432Ter | stop_gained | 10/15 | ENST00000647874.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALOX12B | ENST00000647874.1 | c.1294C>T | p.Arg432Ter | stop_gained | 10/15 | NM_001139.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000127 AC: 2AN: 156936Hom.: 0 AF XY: 0.0000121 AC XY: 1AN XY: 82484
GnomAD4 exome AF: 0.0000265 AC: 37AN: 1398326Hom.: 0 Cov.: 33 AF XY: 0.0000290 AC XY: 20AN XY: 689668
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Autosomal recessive congenital ichthyosis 2 Pathogenic:3
Pathogenic, no assertion criteria provided | clinical testing | Institute for Human Genetics, University Medical Center Freiburg | Jan 07, 2021 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2005 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | The ALOX12B c.1294C>T (p.Arg432Ter) variant is a stop-gained variant. The p.Arg432Ter variant has been reported in two studies and identified in three individuals with congenital ichthyosis in a compound heterozygous state, two of whom were related (Eckl et al. 2005; Akiyama et al. 2010). The p.Arg432Ter variant was absent from 250 ethnically-matched controls and is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium. Due to the potential impact of stop-gained variants and limited evidence, the p.Arg432Ter variant is classified as likely pathogenic for congenital ichthyosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 06, 2018 | The R432X pathogenic variant in the ALOX12B gene has been reported previously either in the homozygous state or in combination with another ALOX12B variant in several individuals with congenital ichthyosis (Eckl et al., 2005; Kurban et al., 2010; Buckova et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R432X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R432X as a pathogenic variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at