rs555408487
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The ENST00000216392.8(PYGL):c.2110G>A(p.Ala704Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A704A) has been classified as Benign.
Frequency
Consequence
ENST00000216392.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PYGL | NM_002863.5 | c.2110G>A | p.Ala704Thr | missense_variant | 17/20 | ENST00000216392.8 | NP_002854.3 | |
PYGL | NM_001163940.2 | c.2008G>A | p.Ala670Thr | missense_variant | 16/19 | NP_001157412.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PYGL | ENST00000216392.8 | c.2110G>A | p.Ala704Thr | missense_variant | 17/20 | 1 | NM_002863.5 | ENSP00000216392 | P1 | |
PYGL | ENST00000532462.5 | c.2110G>A | p.Ala704Thr | missense_variant | 17/20 | 1 | ENSP00000431657 | |||
PYGL | ENST00000544180.6 | c.2008G>A | p.Ala670Thr | missense_variant | 16/19 | 2 | ENSP00000443787 | |||
PYGL | ENST00000532107.2 | n.283G>A | non_coding_transcript_exon_variant | 2/4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251472Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135904
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727246
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74492
ClinVar
Submissions by phenotype
Glycogen storage disease, type VI Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 11, 2018 | This variant has not been reported in the literature in individuals with PYGL-related disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 704 of the PYGL protein (p.Ala704Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at