rs57666183
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001330691.3(CEP78):āc.2007T>Cā(p.Cys669=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 1,613,602 control chromosomes in the GnomAD database, including 169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.019 ( 85 hom., cov: 32)
Exomes š: 0.0020 ( 84 hom. )
Consequence
CEP78
NM_001330691.3 synonymous
NM_001330691.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.18
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
Variant 9-78266603-T-C is Benign according to our data. Variant chr9-78266603-T-C is described in ClinVar as [Benign]. Clinvar id is 517542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.18 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP78 | NM_001330691.3 | c.2007T>C | p.Cys669= | synonymous_variant | 16/17 | ENST00000643273.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP78 | ENST00000643273.2 | c.2007T>C | p.Cys669= | synonymous_variant | 16/17 | NM_001330691.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0192 AC: 2927AN: 152128Hom.: 84 Cov.: 32
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GnomAD3 exomes AF: 0.00517 AC: 1282AN: 247978Hom.: 37 AF XY: 0.00395 AC XY: 532AN XY: 134576
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GnomAD4 exome AF: 0.00199 AC: 2909AN: 1461356Hom.: 84 Cov.: 31 AF XY: 0.00176 AC XY: 1278AN XY: 726948
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GnomAD4 genome ? AF: 0.0193 AC: 2935AN: 152246Hom.: 85 Cov.: 32 AF XY: 0.0185 AC XY: 1380AN XY: 74454
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 23, 2017 | p.Cys670Cys in exon 16 of CEP78: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 7.49% (684/9138) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs57666183). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at