rs1555134900
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_Strong
The ENST00000164139.4(PYGM):c.1463C>T(p.Thr488Ile) 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. 13/21 in silico tools predict a damaging 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. T488N) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000164139.4 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PYGM | NM_005609.4 | c.1463C>T | p.Thr488Ile | missense_variant | 12/20 | ENST00000164139.4 | NP_005600.1 | |
PYGM | NM_001164716.1 | c.1199C>T | p.Thr400Ile | missense_variant | 10/18 | NP_001158188.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PYGM | ENST00000164139.4 | c.1463C>T | p.Thr488Ile | missense_variant | 12/20 | 1 | NM_005609.4 | ENSP00000164139 | P1 | |
PYGM | ENST00000377432.7 | c.1199C>T | p.Thr400Ile | missense_variant | 10/18 | 2 | ENSP00000366650 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 01, 2023 | Variant summary: PYGM c.1463C>T (p.Thr488Ile) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251482 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1463C>T has been reported in the literature in at least one compund heterozygous individual affected with Glycogen Storage Disease, Type V (e.g., Aquaron_2007). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 17324573). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Glycogen storage disease, type V Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.