rs761908536
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000158.4(GBE1):āc.1988T>Cā(p.Leu663Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,612,206 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 (ā ā ). Synonymous variant affecting the same amino acid position (i.e. L663L) has been classified as Likely benign.
Frequency
Consequence
NM_000158.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GBE1 | NM_000158.4 | c.1988T>C | p.Leu663Pro | missense_variant | 15/16 | ENST00000429644.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GBE1 | ENST00000429644.7 | c.1988T>C | p.Leu663Pro | missense_variant | 15/16 | 1 | NM_000158.4 | P1 | |
GBE1 | ENST00000489715.1 | c.1865T>C | p.Leu622Pro | missense_variant | 15/16 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000526 AC: 13AN: 246990Hom.: 0 AF XY: 0.0000747 AC XY: 10AN XY: 133950
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1459994Hom.: 0 Cov.: 29 AF XY: 0.0000372 AC XY: 27AN XY: 726164
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74358
ClinVar
Submissions by phenotype
Glycogen storage disease, type IV Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Adult polyglucosan body disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2016 | - - |
Glycogen storage disease, type IV;C1856301:Glycogen storage disease IV, classic hepatic Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 663 of the GBE1 protein (p.Leu663Pro). This variant is present in population databases (rs761908536, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GBE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 526615). 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 GBE1 protein function. 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