rs119103256
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005609.4(PYGM):c.1996C>T(p.Gln666Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,846 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
PYGM
NM_005609.4 stop_gained
NM_005609.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 9.96
Genes affected
PYGM (HGNC:9726): (glycogen phosphorylase, muscle associated) This gene encodes a muscle enzyme involved in glycogenolysis. Highly similar enzymes encoded by different genes are found in liver and brain. Mutations in this gene are associated with McArdle disease (myophosphorylase deficiency), a glycogen storage disease of muscle. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 11-64750557-G-A is Pathogenic according to our data. Variant chr11-64750557-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2995430.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PYGM | NM_005609.4 | c.1996C>T | p.Gln666Ter | stop_gained | 17/20 | ENST00000164139.4 | |
PYGM | NM_001164716.1 | c.1732C>T | p.Gln578Ter | stop_gained | 15/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PYGM | ENST00000164139.4 | c.1996C>T | p.Gln666Ter | stop_gained | 17/20 | 1 | NM_005609.4 | P1 | |
PYGM | ENST00000377432.7 | c.1732C>T | p.Gln578Ter | stop_gained | 15/18 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151846Hom.: 0 Cov.: 32
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GnomAD4 exome Cov.: 32
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GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151846Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74176
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Glycogen storage disease, type V Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | This sequence change creates a premature translational stop signal (p.Gln666*) in the PYGM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PYGM are known to be pathogenic (PMID: 8316268, 16786513). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PYGM-related conditions. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at