4-106095511-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001163435.3(TBCK):c.2542G>A(p.Val848Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001163435.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TBCK | NM_001163435.3 | c.2542G>A | p.Val848Met | missense_variant | Exon 25 of 26 | ENST00000394708.7 | NP_001156907.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251208Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135766
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461620Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727110
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74348
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.2542G>A (p.V848M) alteration is located in exon 25 (coding exon 24) of the TBCK gene. This alteration results from a G to A substitution at nucleotide position 2542, causing the valine (V) at amino acid position 848 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 848 of the TBCK protein (p.Val848Met). This variant is present in population databases (rs369393998, gnomAD 0.004%). 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: 1508750). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TBCK protein function with a negative predictive value of 80%. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at