9-36227253-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001128227.3(GNE):āc.1369A>Cā(p.Met457Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000187 in 1,606,496 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 ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M457T) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNE | NM_001128227.3 | c.1369A>C | p.Met457Leu | missense_variant | 7/12 | ENST00000396594.8 | |
GNE | NM_005476.7 | c.1276A>C | p.Met426Leu | missense_variant | 7/12 | ENST00000642385.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNE | ENST00000396594.8 | c.1369A>C | p.Met457Leu | missense_variant | 7/12 | 1 | NM_001128227.3 | ||
GNE | ENST00000642385.2 | c.1276A>C | p.Met426Leu | missense_variant | 7/12 | NM_005476.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251442Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135898
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1454314Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 723978
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74338
ClinVar
Submissions by phenotype
Sialuria;C1853926:GNE myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 30, 2021 | This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 457 of the GNE protein (p.Met457Leu). This variant is present in population databases (rs750404513, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with GNE-related conditions. ClinVar contains an entry for this variant (Variation ID: 284972). 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 GNE 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 11, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at