rs147398904
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 8P and 5B. PVS1BS1_SupportingBS2
The NM_014956.5(CEP164):c.4228C>T(p.Gln1410Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,614,176 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_014956.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP164 | NM_014956.5 | c.4228C>T | p.Gln1410Ter | stop_gained | 32/33 | ENST00000278935.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP164 | ENST00000278935.8 | c.4228C>T | p.Gln1410Ter | stop_gained | 32/33 | 1 | NM_014956.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00105 AC: 160AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000813 AC: 204AN: 250978Hom.: 0 AF XY: 0.000730 AC XY: 99AN XY: 135676
GnomAD4 exome AF: 0.00202 AC: 2949AN: 1461856Hom.: 2 Cov.: 31 AF XY: 0.00190 AC XY: 1380AN XY: 727228
GnomAD4 genome AF: 0.00105 AC: 160AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.000926 AC XY: 69AN XY: 74488
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 07, 2015 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 08, 2023 | Identified in trans with another CEP164 variant in a patient with non-cystic fibrosis related bronchiectasis, hearing aids, recurrent ear infections, rhinitis, BMI of 28, and mild learning disabilities; this patient also harbored variants in other potentially causative genes (Devlin et al., 2022); Observed heterozygous in a patient with cone dystrophy in published literature (Bryant et al., 2018) who had a different genetic etiology for the phenotype; Reported previously as a candidate for pancreatic cancer susceptibility, however, clinical history and familial segregation information were not included (Smith et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 33111339, 22863007, 34556108, 29343940, 36273371, 31345219, 35728977, 26546047) - |
Nephronophthisis 15 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 28, 2022 | This sequence change creates a premature translational stop signal (p.Gln1410*) in the CEP164 gene. However, it is currently unclear if variants that occur in this region of the gene cause disease. This variant is present in population databases (rs147398904, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CEP164-related conditions. ClinVar contains an entry for this variant (Variation ID: 281163). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 12, 2022 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Retinal dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Blueprint Genetics | May 03, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at