rs104894009
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_000162.5(GCK):c.895G>C(p.Gly299Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G299D) has been classified as Uncertain significance.
Frequency
Consequence
NM_000162.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GCK | NM_000162.5 | c.895G>C | p.Gly299Arg | missense_variant | 8/10 | ENST00000403799.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GCK | ENST00000403799.8 | c.895G>C | p.Gly299Arg | missense_variant | 8/10 | 1 | NM_000162.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 33
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Maturity-onset diabetes of the young type 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 1992 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 27, 2019 | Not found in the total gnomAD dataset, and the data is high quality. Predicted to have a damaging effect on the protein. Found in multiple individuals with expected phenotype for this gene. Assessment of experimental evidence suggests this variant results in abnormal protein function. Very strong co-segregation with disease, and data include affected and unaffected individuals from multiple families. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at