rs5458
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_002103.5(GYS1):āc.420A>Gā(p.Gly140=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,613,178 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.012 ( 30 hom., cov: 32)
Exomes š: 0.0023 ( 59 hom. )
Consequence
GYS1
NM_002103.5 synonymous
NM_002103.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.201
Genes affected
GYS1 (HGNC:4706): (glycogen synthase 1) The protein encoded by this gene catalyzes the addition of glucose monomers to the growing glycogen molecule through the formation of alpha-1,4-glycoside linkages. Mutations in this gene are associated with muscle glycogen storage disease. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 19-48987266-T-C is Benign according to our data. Variant chr19-48987266-T-C is described in ClinVar as [Benign]. Clinvar id is 329824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.201 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1838/152208) while in subpopulation AFR AF= 0.0367 (1524/41518). AF 95% confidence interval is 0.0352. There are 30 homozygotes in gnomad4. There are 835 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 30 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GYS1 | NM_002103.5 | c.420A>G | p.Gly140= | synonymous_variant | 3/16 | ENST00000323798.8 | |
GYS1 | NM_001161587.2 | c.301-1231A>G | intron_variant | ||||
GYS1 | NR_027763.2 | n.435A>G | non_coding_transcript_exon_variant | 2/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GYS1 | ENST00000323798.8 | c.420A>G | p.Gly140= | synonymous_variant | 3/16 | 1 | NM_002103.5 | P1 | |
GYS1 | ENST00000263276.6 | c.301-1231A>G | intron_variant | 1 | |||||
GYS1 | ENST00000457974.1 | n.646A>G | non_coding_transcript_exon_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0120 AC: 1832AN: 152090Hom.: 30 Cov.: 32
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GnomAD3 exomes AF: 0.00487 AC: 1211AN: 248812Hom.: 22 AF XY: 0.00395 AC XY: 531AN XY: 134508
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GnomAD4 exome AF: 0.00230 AC: 3359AN: 1460970Hom.: 59 Cov.: 31 AF XY: 0.00215 AC XY: 1565AN XY: 726654
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GnomAD4 genome ? AF: 0.0121 AC: 1838AN: 152208Hom.: 30 Cov.: 32 AF XY: 0.0112 AC XY: 835AN XY: 74428
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Glycogen storage disease due to muscle and heart glycogen synthase deficiency Benign:3
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 | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 19, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 18, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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