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 (★★).
Frequency
Consequence
NM_005609.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PYGM | ENST00000164139.4 | c.2500C>T | p.Arg834Cys | missense_variant | Exon 20 of 20 | 1 | NM_005609.4 | ENSP00000164139.3 | ||
PYGM | ENST00000377432.7 | c.2236C>T | p.Arg746Cys | missense_variant | Exon 18 of 18 | 2 | ENSP00000366650.3 | |||
PYGM | ENST00000483742.1 | n.1853C>T | non_coding_transcript_exon_variant | Exon 3 of 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
- -
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. ClinVar contains an entry for this variant (Variation ID: 2197078). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PYGM protein function with a negative predictive value of 80%. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at