X-154379554-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The ENST00000369842.9(EMD):c.70G>A(p.Gly24Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. Synonymous variant affecting the same amino acid position (i.e. G24G) has been classified as Likely benign.
Frequency
Consequence
ENST00000369842.9 missense
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EMD | NM_000117.3 | c.70G>A | p.Gly24Arg | missense_variant | 1/6 | ENST00000369842.9 | NP_000108.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EMD | ENST00000369842.9 | c.70G>A | p.Gly24Arg | missense_variant | 1/6 | 1 | NM_000117.3 | ENSP00000358857 | P1 |
Frequencies
GnomAD3 genomes Cov.: 26
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 26
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 29, 2013 | The Gly24Arg variant in EMD has not been reported in individuals with cardiomyop athy. Data from large population studies is insufficient to assess the frequency of this variant. Computational analyses (biochemical amino acid properties, con servation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully asse ss the clinical significance of the Gly24Arg variant. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 11, 2021 | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID #179103; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (Stenson et al., 2014) - |
X-linked Emery-Dreifuss muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 03, 2023 | ClinVar contains an entry for this variant (Variation ID: 179103). 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. 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 expected to disrupt EMD protein function. This variant has not been reported in the literature in individuals affected with EMD-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 24 of the EMD protein (p.Gly24Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at