chr14-50915869-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_002863.5(PYGL):c.1195C>G(p.Arg399Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R399Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_002863.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PYGL | NM_002863.5 | c.1195C>G | p.Arg399Gly | missense_variant | 10/20 | ENST00000216392.8 | |
PYGL | NM_001163940.2 | c.1093C>G | p.Arg365Gly | missense_variant | 9/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PYGL | ENST00000216392.8 | c.1195C>G | p.Arg399Gly | missense_variant | 10/20 | 1 | NM_002863.5 | P1 | |
PYGL | ENST00000532462.5 | c.1195C>G | p.Arg399Gly | missense_variant | 10/20 | 1 | |||
PYGL | ENST00000544180.6 | c.1093C>G | p.Arg365Gly | missense_variant | 9/19 | 2 | |||
PYGL | ENST00000528757.2 | n.72C>G | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Glycogen storage disease, type VI Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with PYGL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 399 of the PYGL protein (p.Arg399Gly). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.