rs772194378
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_005609.4(PYGM):βc.13_14delβ(p.Leu5ValfsTer22) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. L5L) has been classified as Likely benign.
Frequency
Consequence
NM_005609.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PYGM | NM_005609.4 | c.13_14del | p.Leu5ValfsTer22 | frameshift_variant | 1/20 | ENST00000164139.4 | |
PYGM | NM_001164716.1 | c.13_14del | p.Leu5ValfsTer22 | frameshift_variant | 1/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PYGM | ENST00000164139.4 | c.13_14del | p.Leu5ValfsTer22 | frameshift_variant | 1/20 | 1 | NM_005609.4 | P1 | |
PYGM | ENST00000377432.7 | c.13_14del | p.Leu5ValfsTer22 | frameshift_variant | 1/18 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251176Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135810
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461764Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727176
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74492
ClinVar
Submissions by phenotype
Glycogen storage disease, type V Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 29, 2023 | This sequence change creates a premature translational stop signal (p.Leu5Valfs*22) 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 present in population databases (rs772194378, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with glycogen storage disease (PMID: 17172620). ClinVar contains an entry for this variant (Variation ID: 371064). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jun 21, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at