rs863225191
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001382391.1(CSPP1):c.2463_2469delAGAAGAA(p.Glu822LysfsTer17) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000372 in 1,612,664 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
CSPP1
NM_001382391.1 frameshift
NM_001382391.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.93
Genes affected
CSPP1 (HGNC:26193): (centrosome and spindle pole associated protein 1) This gene encodes a centrosome and spindle pole associated protein. The encoded protein plays a role in cell-cycle progression and spindle organization, regulates cytokinesis, interacts with Nephrocystin 8 and is required for cilia formation. Mutations in this gene result in primary cilia abnormalities and classical Joubert syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Apr 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 8-67159049-AAAGAAAG-A is Pathogenic according to our data. Variant chr8-67159049-AAAGAAAG-A is described in ClinVar as [Pathogenic]. Clinvar id is 217651.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-67159049-AAAGAAAG-A is described in Lovd as [Pathogenic]. Variant chr8-67159049-AAAGAAAG-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CSPP1 | NM_001382391.1 | c.2463_2469delAGAAGAA | p.Glu822LysfsTer17 | frameshift_variant | Exon 21 of 31 | ENST00000678616.1 | NP_001369320.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CSPP1 | ENST00000678616.1 | c.2463_2469delAGAAGAA | p.Glu822LysfsTer17 | frameshift_variant | Exon 21 of 31 | NM_001382391.1 | ENSP00000504733.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000812 AC: 2AN: 246282Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 133894
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460426Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 726528
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74380
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Joubert syndrome 21 Pathogenic:1
Feb 23, 2015
UW Hindbrain Malformation Research Program, University of Washington
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: research
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Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at