rs61736659
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_005609.4(PYGM):c.1957C>G(p.Leu653Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000507 in 1,614,182 control chromosomes in the GnomAD database, including 5 homozygotes. 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 0.00064 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00049 ( 5 hom. )
Consequence
PYGM
NM_005609.4 missense
NM_005609.4 missense
Scores
4
6
7
Clinical Significance
Conservation
PhyloP100: 3.48
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.025466383).
BP6
?
Variant 11-64751337-G-C is Benign according to our data. Variant chr11-64751337-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 95295.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=2, Likely_benign=1}.
BS2
?
High Homozygotes in GnomAdExome at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PYGM | NM_005609.4 | c.1957C>G | p.Leu653Val | missense_variant | 16/20 | ENST00000164139.4 | |
PYGM | NM_001164716.1 | c.1693C>G | p.Leu565Val | missense_variant | 14/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PYGM | ENST00000164139.4 | c.1957C>G | p.Leu653Val | missense_variant | 16/20 | 1 | NM_005609.4 | P1 | |
PYGM | ENST00000377432.7 | c.1693C>G | p.Leu565Val | missense_variant | 14/18 | 2 | |||
PYGM | ENST00000462303.1 | n.281C>G | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000644 AC: 98AN: 152238Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
98
AN:
152238
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000923 AC: 232AN: 251372Hom.: 3 AF XY: 0.000846 AC XY: 115AN XY: 135896
GnomAD3 exomes
AF:
AC:
232
AN:
251372
Hom.:
AF XY:
AC XY:
115
AN XY:
135896
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000493 AC: 720AN: 1461826Hom.: 5 Cov.: 31 AF XY: 0.000458 AC XY: 333AN XY: 727218
GnomAD4 exome
AF:
AC:
720
AN:
1461826
Hom.:
Cov.:
31
AF XY:
AC XY:
333
AN XY:
727218
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000643 AC: 98AN: 152356Hom.: 0 Cov.: 32 AF XY: 0.000564 AC XY: 42AN XY: 74504
GnomAD4 genome
?
AF:
AC:
98
AN:
152356
Hom.:
Cov.:
32
AF XY:
AC XY:
42
AN XY:
74504
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
0
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
9
ExAC
?
AF:
AC:
86
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:2Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Glycogen storage disease, type V Uncertain:1Benign:3
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jul 16, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 14, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 15, 2021 | The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25914343) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 11, 2013 | - - |
Tip-toe gait Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking c/o Practice Pomarino | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
0.029
.;B
Vest4
MVP
MPC
0.84
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at