chr8-67164395-GAA-G
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001382391.1(CSPP1):c.2722_2723delAA(p.Asn908CysfsTer14) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000292 in 1,370,364 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000029 ( 0 hom. )
Consequence
CSPP1
NM_001382391.1 frameshift
NM_001382391.1 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.28
Publications
0 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]
CSPP1 Gene-Disease associations (from GenCC):
- Joubert syndrome 21Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
- Joubert syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Joubert syndrome with Jeune asphyxiating thoracic dystrophyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Meckel syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 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;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CSPP1 | NM_001382391.1 | c.2722_2723delAA | p.Asn908CysfsTer14 | frameshift_variant | Exon 24 of 31 | ENST00000678616.1 | NP_001369320.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CSPP1 | ENST00000678616.1 | c.2722_2723delAA | p.Asn908CysfsTer14 | frameshift_variant | Exon 24 of 31 | NM_001382391.1 | ENSP00000504733.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000292 AC: 4AN: 1370364Hom.: 0 AF XY: 0.00000146 AC XY: 1AN XY: 686840 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
4
AN:
1370364
Hom.:
AF XY:
AC XY:
1
AN XY:
686840
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
31666
American (AMR)
AF:
AC:
0
AN:
44022
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25416
East Asian (EAS)
AF:
AC:
0
AN:
39248
South Asian (SAS)
AF:
AC:
0
AN:
83502
European-Finnish (FIN)
AF:
AC:
0
AN:
53036
Middle Eastern (MID)
AF:
AC:
0
AN:
5580
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1030820
Other (OTH)
AF:
AC:
0
AN:
57074
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.002091), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.363
Heterozygous variant carriers
0
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1
2
2
3
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0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
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50-55
55-60
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>80
Age
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational 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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