rs796052128
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001329943.3(KIAA0586):c.1000C>T(p.Gln334Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,222 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001329943.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIAA0586 | NM_001329943.3 | c.1000C>T | p.Gln334Ter | stop_gained | 8/31 | ENST00000652326.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIAA0586 | ENST00000652326.2 | c.1000C>T | p.Gln334Ter | stop_gained | 8/31 | NM_001329943.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 246764Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 133982
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1458222Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 725416
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Joubert syndrome 23 Pathogenic:2
Pathogenic, criteria provided, single submitter | research | UW Hindbrain Malformation Research Program, University of Washington | Sep 01, 2015 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 11, 2015 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jan 26, 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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26386044, 28497568, 26096313) - |
KIAA0586-related condition Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 27, 2022 | The KIAA0586 c.1159C>T variant is predicted to result in premature protein termination (p.Gln387*). This variant along with second allele in KIAA0586 was reported in two individuals with Joubert syndrome (Table 1, Bachmann-Gagescu et al 2015. PubMed ID: 26096313; reported as p.Gln334* in Table S2, Summers et al 2017. PubMed ID: 28497568). This variant is reported in 0.00089% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-58917335-C-T). In ClinVar, this variant is reported as pathogenic (https://preview.ncbi.nlm.nih.gov/clinvar/variation/204595/). Nonsense variants in KIAA0586 are expected to be pathogenic. This variant is interpreted as pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at