rs547681142
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020964.3(EPG5):c.6792G>T(p.Met2264Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000297 in 1,614,224 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 nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M2264T) has been classified as Uncertain significance.
Frequency
Consequence
NM_020964.3 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 |
---|---|---|---|---|---|---|---|
EPG5 | NM_020964.3 | c.6792G>T | p.Met2264Ile | missense_variant | 40/44 | ENST00000282041.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPG5 | ENST00000282041.11 | c.6792G>T | p.Met2264Ile | missense_variant | 40/44 | 1 | NM_020964.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249192Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135230
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727242
GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152342Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74494
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 06, 2023 | The c.6792G>T (p.M2264I) alteration is located in exon 40 (coding exon 40) of the EPG5 gene. This alteration results from a G to T substitution at nucleotide position 6792, causing the methionine (M) at amino acid position 2264 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 26, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Vici syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 20, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2264 of the EPG5 protein (p.Met2264Ile). This variant is present in population databases (rs547681142, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with EPG5-related conditions. ClinVar contains an entry for this variant (Variation ID: 534595). 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 EPG5 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