rs1187839124
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_201548.5(CERKL):c.1303C>T(p.Arg435Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000498 in 1,607,330 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R435R) has been classified as Likely benign. 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 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CERKL | NM_201548.5 | c.1303C>T | p.Arg435Ter | stop_gained | 11/13 | ENST00000410087.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CERKL | ENST00000410087.8 | c.1303C>T | p.Arg435Ter | stop_gained | 11/13 | 1 | NM_201548.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151846Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248850Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134500
GnomAD4 exome AF: 0.00000481 AC: 7AN: 1455484Hom.: 0 Cov.: 28 AF XY: 0.00000414 AC XY: 3AN XY: 724020
GnomAD4 genome AF: 0.00000659 AC: 1AN: 151846Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74144
ClinVar
Submissions by phenotype
Retinitis pigmentosa 26 Pathogenic:4
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Nov 28, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 05, 2023 | - - |
not provided Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen | Oct 23, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | This sequence change creates a premature translational stop signal (p.Arg461*) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 28559085). ClinVar contains an entry for this variant (Variation ID: 555316). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2019 | - - |
Retinal dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Apr 02, 2019 | - - |
Retinitis pigmentosa Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Nov 04, 2018 | The CERKL c.1303C>T (p.Arg435Ter) variant is a stop-gained variant that is expected to result in an absent or truncated protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is reported at a frequency of 0.000115 in the African population of the Genome Aggregation Database, but this frequency is based on one allele only in a region of good sequencing coverage. The variant is therefore presumed to be rare. Based on the potential impact of stop-gained variants and the lack of clarifying evidence, the p.Arg435Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at