rs587777141
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001382391.1(CSPP1):c.3227dupA(p.Tyr1076fs) variant causes a frameshift, stop gained 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
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
CSPP1
NM_001382391.1 frameshift, stop_gained
NM_001382391.1 frameshift, stop_gained
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.36
Publications
2 publications found
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]
ARFGEF1 (HGNC:15772): (ADP ribosylation factor guanine nucleotide exchange factor 1) ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP. It contains a Sec7 domain, which may be responsible for guanine-nucleotide exchange activity and also brefeldin A inhibition. [provided by RefSeq, Aug 2011]
ARFGEF1 Gene-Disease associations (from GenCC):
- developmental delay, impaired speech, and behavioral abnormalities, with or without seizuresInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae)
- schizophreniaInheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 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 8-67190655-T-TA is Pathogenic according to our data. Variant chr8-67190655-T-TA is described in ClinVar as Pathogenic. ClinVar VariationId is 100669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001382391.1. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CSPP1 | NM_001382391.1 | MANE Select | c.3227dupA | p.Tyr1076fs | frameshift stop_gained | Exon 29 of 31 | NP_001369320.1 | A0A7I2V5W3 | |
| CSPP1 | NM_001364869.1 | c.3293dupA | p.Tyr1098fs | frameshift stop_gained | Exon 28 of 30 | NP_001351798.1 | A0A7I2PHE7 | ||
| CSPP1 | NM_024790.7 | c.3212dupA | p.Tyr1071fs | frameshift stop_gained | Exon 27 of 29 | NP_079066.5 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CSPP1 | ENST00000678616.1 | MANE Select | c.3227dupA | p.Tyr1076fs | frameshift stop_gained | Exon 29 of 31 | ENSP00000504733.1 | A0A7I2V5W3 | |
| CSPP1 | ENST00000262210.11 | TSL:1 | c.3293dupA | p.Tyr1098fs | frameshift stop_gained | Exon 28 of 30 | ENSP00000262210.6 | A0A7I2PHE7 | |
| CSPP1 | ENST00000519668.1 | TSL:1 | c.2177dupA | p.Tyr726fs | frameshift stop_gained | Exon 24 of 26 | ENSP00000430092.1 | Q1MSJ5-2 |
Frequencies
GnomAD3 genomes
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 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461492
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
727104
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33472
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
1
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
53416
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111642
Other (OTH)
AF:
AC:
0
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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30-35
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
4
-
-
Joubert syndrome 21 (4)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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