14-50944251-G-A
Position:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_002863.5(PYGL):c.153C>T(p.Asp51=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 1,613,776 control chromosomes in the GnomAD database, including 2,021 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.068 ( 541 hom., cov: 33)
Exomes 𝑓: 0.039 ( 1480 hom. )
Consequence
PYGL
NM_002863.5 synonymous
NM_002863.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.27
Genes affected
PYGL (HGNC:9725): (glycogen phosphorylase L) This gene encodes a homodimeric protein that catalyses the cleavage of alpha-1,4-glucosidic bonds to release glucose-1-phosphate from liver glycogen stores. This protein switches from inactive phosphorylase B to active phosphorylase A by phosphorylation of serine residue 15. Activity of this enzyme is further regulated by multiple allosteric effectors and hormonal controls. Humans have three glycogen phosphorylase genes that encode distinct isozymes that are primarily expressed in liver, brain and muscle, respectively. The liver isozyme serves the glycemic demands of the body in general while the brain and muscle isozymes supply just those tissues. In glycogen storage disease type VI, also known as Hers disease, mutations in liver glycogen phosphorylase inhibit the conversion of glycogen to glucose and results in moderate hypoglycemia, mild ketosis, growth retardation and hepatomegaly. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Feb 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 14-50944251-G-A is Benign according to our data. Variant chr14-50944251-G-A is described in ClinVar as [Benign]. Clinvar id is 193236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-50944251-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=2.27 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PYGL | NM_002863.5 | c.153C>T | p.Asp51= | synonymous_variant | 1/20 | ENST00000216392.8 | |
PYGL | NM_001163940.2 | c.153C>T | p.Asp51= | synonymous_variant | 1/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PYGL | ENST00000216392.8 | c.153C>T | p.Asp51= | synonymous_variant | 1/20 | 1 | NM_002863.5 | P1 | |
PYGL | ENST00000532462.5 | c.153C>T | p.Asp51= | synonymous_variant | 1/20 | 1 | |||
PYGL | ENST00000530336.2 | n.220C>T | non_coding_transcript_exon_variant | 1/5 | 1 | ||||
PYGL | ENST00000544180.6 | c.153C>T | p.Asp51= | synonymous_variant | 1/19 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0676 AC: 10292AN: 152214Hom.: 537 Cov.: 33
GnomAD3 genomes
AF:
AC:
10292
AN:
152214
Hom.:
Cov.:
33
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: 0.0426 AC: 10679AN: 250590Hom.: 369 AF XY: 0.0418 AC XY: 5669AN XY: 135716
GnomAD3 exomes
AF:
AC:
10679
AN:
250590
Hom.:
AF XY:
AC XY:
5669
AN XY:
135716
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: 0.0393 AC: 57387AN: 1461444Hom.: 1480 Cov.: 32 AF XY: 0.0392 AC XY: 28503AN XY: 727076
GnomAD4 exome
AF:
AC:
57387
AN:
1461444
Hom.:
Cov.:
32
AF XY:
AC XY:
28503
AN XY:
727076
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: 0.0677 AC: 10312AN: 152332Hom.: 541 Cov.: 33 AF XY: 0.0666 AC XY: 4959AN XY: 74496
GnomAD4 genome
AF:
AC:
10312
AN:
152332
Hom.:
Cov.:
33
AF XY:
AC XY:
4959
AN XY:
74496
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:
Asia WGS
AF:
AC:
83
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 06, 2015 | - - |
not provided Benign:2
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 12, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 26, 2020 | - - |
Glycogen storage disease, type VI Benign:2
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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