11-64757899-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_005609.4(PYGM):c.540C>T(p.Ala180Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
PYGM
NM_005609.4 synonymous
NM_005609.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.17
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 11-64757899-G-A is Benign according to our data. Variant chr11-64757899-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 259838.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-3.17 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PYGM | NM_005609.4 | c.540C>T | p.Ala180Ala | synonymous_variant | 5/20 | ENST00000164139.4 | NP_005600.1 | |
| PYGM | NM_001164716.1 | c.276C>T | p.Ala92Ala | synonymous_variant | 3/18 | NP_001158188.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PYGM | ENST00000164139.4 | c.540C>T | p.Ala180Ala | synonymous_variant | 5/20 | 1 | NM_005609.4 | ENSP00000164139.3 | ||
| PYGM | ENST00000377432.7 | c.276C>T | p.Ala92Ala | synonymous_variant | 3/18 | 2 | ENSP00000366650.3 |
Frequencies
GnomAD3 genomes 0.0000854 AC: 13AN: 152140Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000677 AC: 17AN: 251056Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135806
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GnomAD4 exome AF: 0.0000472 AC: 69AN: 1461708Hom.: 0 Cov.: 39 AF XY: 0.0000399 AC XY: 29AN XY: 727152
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GnomAD4 genome 0.0000854 AC: 13AN: 152258Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74434
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Glycogen storage disease, type V Uncertain:1Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 16, 2024 | - - |
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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