rs886044839
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BS1_SupportingBS2
The NM_000117.3(EMD):c.502C>T(p.Arg168Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,097,977 control chromosomes in the GnomAD database, including 1 homozygotes. There are 3 hemizygotes in GnomAD. 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. R168H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000117.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EMD | NM_000117.3 | c.502C>T | p.Arg168Cys | missense_variant | 6/6 | ENST00000369842.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EMD | ENST00000369842.9 | c.502C>T | p.Arg168Cys | missense_variant | 6/6 | 1 | NM_000117.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 exomes AF: 0.0000273 AC: 5AN: 182849Hom.: 1 AF XY: 0.00 AC XY: 0AN XY: 67483
GnomAD4 exome AF: 0.0000146 AC: 16AN: 1097977Hom.: 1 Cov.: 32 AF XY: 0.00000826 AC XY: 3AN XY: 363373
GnomAD4 genome ? Cov.: 24
ClinVar
Submissions by phenotype
Emery-Dreifuss muscular dystrophy Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 24, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 04, 2015 | - - |
X-linked Emery-Dreifuss muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 22, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 168 of the EMD protein (p.Arg168Cys). This variant is present in population databases (no rsID available, gnomAD 0.02%), 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: 285132). 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"). 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. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 03, 2023 | The p.R168C variant (also known as c.502C>T), located in coding exon 6 of the EMD gene, results from a C to T substitution at nucleotide position 502. The arginine at codon 168 is replaced by cysteine, an amino acid with highly dissimilar properties. Based on data from gnomAD, the T allele has an overall frequency of 0.003% (5/182849) total alleles studied, with 1 homozygote(s) and no hemizygote(s) observed. The highest observed frequency was 0.02% (4/19080) of South Asian alleles. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at