rs1057518332
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001163435.3(TBCK):c.1771C>T(p.Gln591Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000491 in 1,425,902 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 Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Q591Q) has been classified as Uncertain significance. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001163435.3 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 |
---|---|---|---|---|---|---|---|
TBCK | NM_001163435.3 | c.1771C>T | p.Gln591Ter | stop_gained | 19/26 | ENST00000394708.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBCK | ENST00000394708.7 | c.1771C>T | p.Gln591Ter | stop_gained | 19/26 | 1 | NM_001163435.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 247074Hom.: 0 AF XY: 0.00000748 AC XY: 1AN XY: 133756
GnomAD4 exome AF: 0.00000491 AC: 7AN: 1425902Hom.: 0 Cov.: 27 AF XY: 0.00000141 AC XY: 1AN XY: 710278
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 30, 2016 | The Q591X variant in the TBCK gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q591X variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret Q591X as a likely pathogenic variant. - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change creates a premature translational stop signal (p.Gln591*) in the TBCK gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TBCK are known to be pathogenic (PMID: 27040692, 30103036). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with TBCK-related conditions. ClinVar contains an entry for this variant (Variation ID: 373291). For these reasons, this variant has been classified as Pathogenic. - |
Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota | Mar 27, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at