chr11-117338596-C-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_014956.5(CEP164):c.10C>T(p.Arg4Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R4R) has been classified as Likely benign.
Frequency
Consequence
NM_014956.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP164 | NM_014956.5 | c.10C>T | p.Arg4Ter | stop_gained | 3/33 | ENST00000278935.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP164 | ENST00000278935.8 | c.10C>T | p.Arg4Ter | stop_gained | 3/33 | 1 | NM_014956.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251422Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135880
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461698Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727158
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74306
ClinVar
Submissions by phenotype
Nephronophthisis 15 Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jun 30, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 11, 2023 | This sequence change creates a premature translational stop signal (p.Arg4*) in the CEP164 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP164 are known to be pathogenic (PMID: 22863007, 28125082, 32367404, 34132027, 34499853). This variant is present in population databases (rs765277720, gnomAD 0.01%). 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: 1064314). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 21, 2022 | 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; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at