rs398122963
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_201548.5(CERKL):c.598A>T(p.Lys200Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,612,486 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 (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_201548.5 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 |
---|---|---|---|---|---|---|---|
CERKL | NM_201548.5 | c.598A>T | p.Lys200Ter | stop_gained | 3/13 | ENST00000410087.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CERKL | ENST00000410087.8 | c.598A>T | p.Lys200Ter | stop_gained | 3/13 | 1 | NM_201548.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250424Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135412
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460304Hom.: 0 Cov.: 29 AF XY: 0.0000151 AC XY: 11AN XY: 726484
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74360
ClinVar
Submissions by phenotype
Retinitis pigmentosa 26 Pathogenic:3
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 11, 2020 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2013 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 26, 2023 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | This sequence change creates a premature translational stop signal (p.Lys200*) in the CERKL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CERKL are known to be pathogenic (PMID: 14681825, 23591405, 24043777). This variant is present in population databases (rs398122963, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with inherited retinal dystrophy (PMID: 24043777, 25097241). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 91393). For these reasons, this variant has been classified as Pathogenic. - |
Retinitis pigmentosa Pathogenic:1
Pathogenic, criteria provided, single submitter | curation | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | Apr 01, 2021 | The p.Lys200Ter variant in CERKL was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PM3-P. Based on this evidence we have classified this variant as Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at