3-52290379-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_145262.4(GLYCTK):c.37C>T(p.Arg13*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,602,946 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).
Frequency
Consequence
NM_145262.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152232Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000145 AC: 21AN: 1450714Hom.: 0 Cov.: 31 AF XY: 0.0000125 AC XY: 9AN XY: 722074
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74364
ClinVar
Submissions by phenotype
D-Glyceric aciduria Pathogenic:1Uncertain:1
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Variant summary: GLYCTK c.37C>T (p.Arg13X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic in ClinVar and is associated with D-glyceric aciduria in HGMD. The variant was absent in 236634 control chromosomes (gnomAD). To our knowledge c.37C>T has not been reported in the literature in individuals affected with D-Glyceric Aciduria and no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. -
not provided Uncertain:1
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. This variant has not been reported in the literature in individuals affected with GLYCTK-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.005%). This sequence change creates a premature translational stop signal (p.Arg13*) in the GLYCTK gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in GLYCTK cause disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at