rs150483902
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM5BP4_StrongBP6_Very_StrongBS1BS2
The NM_002863.5(PYGL):c.176C>T(p.Thr59Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00087 in 1,613,148 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T59K) has been classified as Likely pathogenic.
Frequency
Consequence
NM_002863.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PYGL | NM_002863.5 | c.176C>T | p.Thr59Met | missense_variant | 1/20 | ENST00000216392.8 | |
PYGL | NM_001163940.2 | c.176C>T | p.Thr59Met | missense_variant | 1/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PYGL | ENST00000216392.8 | c.176C>T | p.Thr59Met | missense_variant | 1/20 | 1 | NM_002863.5 | P1 | |
PYGL | ENST00000532462.5 | c.176C>T | p.Thr59Met | missense_variant | 1/20 | 1 | |||
PYGL | ENST00000530336.2 | n.243C>T | non_coding_transcript_exon_variant | 1/5 | 1 | ||||
PYGL | ENST00000544180.6 | c.176C>T | p.Thr59Met | missense_variant | 1/19 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00465 AC: 708AN: 152236Hom.: 5 Cov.: 33
GnomAD3 exomes AF: 0.00133 AC: 333AN: 249758Hom.: 4 AF XY: 0.000953 AC XY: 129AN XY: 135420
GnomAD4 exome AF: 0.000474 AC: 693AN: 1460794Hom.: 7 Cov.: 31 AF XY: 0.000402 AC XY: 292AN XY: 726790
GnomAD4 genome AF: 0.00467 AC: 711AN: 152354Hom.: 5 Cov.: 33 AF XY: 0.00438 AC XY: 326AN XY: 74506
ClinVar
Submissions by phenotype
Glycogen storage disease, type VI Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 21, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 28, 2023 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 06, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at