rs587777141
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001382391.1(CSPP1):c.3227dup(p.Tyr1076Ter) variant causes a stop gained, frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,492 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Y1076Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001382391.1 stop_gained, 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 | UniProt |
---|---|---|---|---|---|---|---|
CSPP1 | NM_001382391.1 | c.3227dup | p.Tyr1076Ter | stop_gained, frameshift_variant | 29/31 | ENST00000678616.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSPP1 | ENST00000678616.1 | c.3227dup | p.Tyr1076Ter | stop_gained, frameshift_variant | 29/31 | NM_001382391.1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461492Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727104
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Joubert syndrome 21 Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2022 | ClinVar contains an entry for this variant (Variation ID: 100669). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with Joubert syndrome and related disorders (PMID: 24360808). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr1071*) in the CSPP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CSPP1 are known to be pathogenic (PMID: 24360807, 24360808). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 02, 2014 | - - |
Pathogenic, criteria provided, single submitter | research | UW Hindbrain Malformation Research Program, University of Washington | Feb 23, 2015 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | DASA | Nov 03, 2022 | The c.3212dup;p.(Tyr1071*) variant creates a premature translational stop signal in the CSPP1 gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 10066; PMID: 24360808) - PS4. This variant is not present in population databases (rs587777141, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at