9-36227253-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001128227.3(GNE):āc.1369A>Gā(p.Met457Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,454,314 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M457L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001128227.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNE | NM_001128227.3 | c.1369A>G | p.Met457Val | missense_variant | 7/12 | ENST00000396594.8 | |
GNE | NM_005476.7 | c.1276A>G | p.Met426Val | missense_variant | 7/12 | ENST00000642385.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNE | ENST00000396594.8 | c.1369A>G | p.Met457Val | missense_variant | 7/12 | 1 | NM_001128227.3 | ||
GNE | ENST00000642385.2 | c.1276A>G | p.Met426Val | missense_variant | 7/12 | NM_005476.7 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000344 AC: 5AN: 1454314Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2AN XY: 723978
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Sialuria;C1853926:GNE myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 24, 2021 | This sequence change replaces methionine with valine at codon 457 of the GNE protein (p.Met457Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with GNE-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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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