rs587783414
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The ENST00000380950.7(CEP152):βc.1155delβ(p.Thr386ProfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. V385V) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000380950.7 frameshift
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CEP152 | NM_001194998.2 | c.1155del | p.Thr386ProfsTer13 | frameshift_variant | 9/27 | ENST00000380950.7 | NP_001181927.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CEP152 | ENST00000380950.7 | c.1155del | p.Thr386ProfsTer13 | frameshift_variant | 9/27 | 1 | NM_001194998.2 | ENSP00000370337 | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000481 AC: 12AN: 249572Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135402
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727232
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Microcephaly 9, primary, autosomal recessive Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 24, 2013 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 15, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 158223). This variant has not been reported in the literature in individuals affected with CEP152-related conditions. This variant is present in population databases (rs587783414, gnomAD 0.04%). This sequence change creates a premature translational stop signal (p.Thr386Profs*13) in the CEP152 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP152 are known to be pathogenic (PMID: 21131973). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at