rs781978021
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong
The NM_000117.3(EMD):c.83G>A(p.Gly28Glu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G28R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000117.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EMD | NM_000117.3 | c.83G>A | p.Gly28Glu | missense_variant, splice_region_variant | 2/6 | ENST00000369842.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EMD | ENST00000369842.9 | c.83G>A | p.Gly28Glu | missense_variant, splice_region_variant | 2/6 | 1 | NM_000117.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 25
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 25
ClinVar
Submissions by phenotype
X-linked Emery-Dreifuss muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | This sequence change replaces glycine with glutamic acid at codon 28 of the EMD protein (p.Gly28Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with EMD-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: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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