8-67095440-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001382391.1(CSPP1):c.631C>T(p.Arg211Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,612,898 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 (★★). Synonymous variant affecting the same amino acid position (i.e. R211R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001382391.1 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 |
---|---|---|---|---|---|---|---|
CSPP1 | NM_001382391.1 | c.631C>T | p.Arg211Ter | stop_gained | 7/31 | ENST00000678616.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSPP1 | ENST00000678616.1 | c.631C>T | p.Arg211Ter | stop_gained | 7/31 | NM_001382391.1 |
Frequencies
GnomAD3 genomes AF: 0.0000396 AC: 6AN: 151368Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000522 AC: 13AN: 249138Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135222
GnomAD4 exome AF: 0.0000281 AC: 41AN: 1461530Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 727098
GnomAD4 genome AF: 0.0000396 AC: 6AN: 151368Hom.: 0 Cov.: 31 AF XY: 0.0000677 AC XY: 5AN XY: 73854
ClinVar
Submissions by phenotype
Joubert syndrome 21 Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 24, 2020 | - - |
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 | Invitae | Oct 05, 2023 | This sequence change creates a premature translational stop signal (p.Arg220*) 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). This variant is present in population databases (rs375113643, gnomAD 0.04%). This premature translational stop signal has been observed in individual(s) with Joubert syndrome (PMID: 24360808). ClinVar contains an entry for this variant (Variation ID: 100672). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at