rs113993984
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_002863.5(PYGL):c.2017G>A(p.Glu673Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002863.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PYGL | ENST00000216392.8 | c.2017G>A | p.Glu673Lys | missense_variant | 17/20 | 1 | NM_002863.5 | ENSP00000216392.7 | ||
PYGL | ENST00000532462.5 | c.2017G>A | p.Glu673Lys | missense_variant | 17/20 | 1 | ENSP00000431657.1 | |||
PYGL | ENST00000544180.6 | c.1915G>A | p.Glu639Lys | missense_variant | 16/19 | 2 | ENSP00000443787.1 | |||
PYGL | ENST00000532107.2 | n.190G>A | non_coding_transcript_exon_variant | 2/4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251462Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135898
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.0000413 AC XY: 30AN XY: 727232
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74340
ClinVar
Submissions by phenotype
Glycogen storage disease, type VI Uncertain:3Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Human Genetics | Aug 27, 2020 | disease causing - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 11, 2021 | This sequence change replaces glutamic acid with lysine at codon 673 of the PYGL protein (p.Glu673Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs113993984, ExAC 0.02%). This variant has been observed in individual(s) with glycogen storage disease type VI (PMID: 17705025). ClinVar contains an entry for this variant (Variation ID: 21332). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jun 11, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at