chr11-64746688-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005609.4(PYGM):c.2500C>T(p.Arg834Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R834G) has been classified as Uncertain significance.
Frequency
Consequence
NM_005609.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PYGM | NM_005609.4 | c.2500C>T | p.Arg834Cys | missense_variant | 20/20 | ENST00000164139.4 | |
PYGM | NM_001164716.1 | c.2236C>T | p.Arg746Cys | missense_variant | 18/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PYGM | ENST00000164139.4 | c.2500C>T | p.Arg834Cys | missense_variant | 20/20 | 1 | NM_005609.4 | P1 | |
PYGM | ENST00000377432.7 | c.2236C>T | p.Arg746Cys | missense_variant | 18/18 | 2 | |||
PYGM | ENST00000483742.1 | n.1853C>T | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251400Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135898
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 727244
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74352
ClinVar
Submissions by phenotype
Glycogen storage disease, type V Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 834 of the PYGM protein (p.Arg834Cys). This variant is present in population databases (rs200118962, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PYGM-related conditions. 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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 | Revvity Omics, Revvity | Feb 08, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at