chrX-154381042-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000117.3(EMD):c.610C>T(p.Arg204Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000014 in 1,210,803 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 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. R204G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000117.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EMD | NM_000117.3 | c.610C>T | p.Arg204Cys | missense_variant | 6/6 | ENST00000369842.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EMD | ENST00000369842.9 | c.610C>T | p.Arg204Cys | missense_variant | 6/6 | 1 | NM_000117.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000177 AC: 2AN: 112733Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34881
GnomAD3 exomes AF: 0.0000218 AC: 4AN: 183163Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67789
GnomAD4 exome AF: 0.0000137 AC: 15AN: 1098070Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1AN XY: 363492
GnomAD4 genome ? AF: 0.0000177 AC: 2AN: 112733Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34881
ClinVar
Submissions by phenotype
Emery-Dreifuss muscular dystrophy Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Emery-Dreifuss muscular dystrophy 1, X-linked Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 13, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 10, 2012 | p.Arg204Cys c.610 CGT>TGT in exon 6 of the EMD gene (NM_000117.2): The Arg204Cys variant in the EMD gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Server reports Arg204Cys was not observed in approximately 6,300 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Arg204Cys results in a semi-conservative amino acid substitution of a positively charged Arginine residue with a neutral, polar Cystein residue, which might affect disulfide bonds. In silico analysis predicts Arg204Cys is probably damaging to the protein structure/function. Nevertheless, the Arg204 residue is not well conserved, as a Cysteine residue is present at this position in horse. Also, no missense mutations in nearby codons have been reported in association with EDMD. With the clinical and molecular information available at this time, we cannot definitively determine if Arg204Cys is a disease-causing mutation or a rare benign variant. The variant is found in DCM panel(s). - |
X-linked Emery-Dreifuss muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 30, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 204 of the EMD protein (p.Arg204Cys). This variant is present in population databases (rs782299893, gnomAD 0.005%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with EMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 201776). 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. 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