rs1057517695
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001330691.3(CEP78):c.534delT(p.Lys179ArgfsTer10) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L178L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CEP78
NM_001330691.3 frameshift
NM_001330691.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.19
Publications
3 publications found
Genes affected
CEP78 (HGNC:25740): (centrosomal protein 78) This gene encodes a centrosomal protein that is both required for the regulation of centrosome-related events during the cell cycle, and required for ciliogenesis. The encoded protein has an N-terminal leucine-rich repeat (LRR) domain with six consecutive LRR repeats, and a C-terminal coiled-coil domain. It interacts with the N-terminal catalytic domain of polo-like kinase 4 (PLK4) and colocalizes with PLK4 to the distal end of the centriole. Naturally occurring mutations in this gene cause defects in primary cilia that result in retinal degeneration and sensorineural hearing loss which are associated with cone-rod degeneration disease as well as Usher syndrome. Low expression of this gene is associated with poor prognosis of colorectal cancer patients. [provided by RefSeq, Mar 2017]
CEP78 Gene-Disease associations (from GenCC):
- cone-rod dystrophy and hearing lossInheritance: Unknown, AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P
- cone-rod dystrophy and hearing loss 1Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- Usher syndrome type 3Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 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 9-78241728-CT-C is Pathogenic according to our data. Variant chr9-78241728-CT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 372270.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001330691.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| CEP78 | MANE Select | c.534delT | p.Lys179ArgfsTer10 | frameshift | Exon 4 of 17 | NP_001317620.1 | Q5JTW2-3 | ||
| CEP78 | c.534delT | p.Lys179ArgfsTer10 | frameshift | Exon 4 of 16 | NP_001092272.1 | Q5JTW2-2 | |||
| CEP78 | c.534delT | p.Lys179ArgfsTer10 | frameshift | Exon 4 of 16 | NP_001336767.1 | A0A2R8YCP0 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CEP78 | MANE Select | c.534delT | p.Lys179ArgfsTer10 | frameshift | Exon 4 of 17 | ENSP00000496423.2 | Q5JTW2-3 | ||
| CEP78 | TSL:1 | c.534delT | p.Lys179ArgfsTer10 | frameshift | Exon 4 of 16 | ENSP00000365782.4 | Q5JTW2-2 | ||
| CEP78 | c.534delT | p.Lys179ArgfsTer10 | frameshift | Exon 4 of 17 | ENSP00000495962.1 | A0A2R8Y7A4 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2AN: 1455038Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1AN XY: 724384 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
2
AN:
1455038
Hom.:
Cov.:
27
AF XY:
AC XY:
1
AN XY:
724384
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33330
American (AMR)
AF:
AC:
0
AN:
44476
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26090
East Asian (EAS)
AF:
AC:
0
AN:
39598
South Asian (SAS)
AF:
AC:
0
AN:
85956
European-Finnish (FIN)
AF:
AC:
0
AN:
53338
Middle Eastern (MID)
AF:
AC:
2
AN:
5758
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1106358
Other (OTH)
AF:
AC:
0
AN:
60134
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
0
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Cone-rod dystrophy and hearing loss 1 (1)
1
-
-
not provided (1)
1
-
-
Sensorineural hearing loss disorder;C4085590:Cone-rod dystrophy (1)
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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