rs782222974
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_000117.3(EMD):c.103G>A(p.Glu35Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000828 in 1,208,250 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. E35E) has been classified as Likely benign.
Frequency
Consequence
NM_000117.3 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 |
---|---|---|---|---|---|---|---|
EMD | NM_000117.3 | c.103G>A | p.Glu35Lys | missense_variant | 2/6 | ENST00000369842.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EMD | ENST00000369842.9 | c.103G>A | p.Glu35Lys | missense_variant | 2/6 | 1 | NM_000117.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000893 AC: 1AN: 112013Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 34189
GnomAD3 exomes AF: 0.0000230 AC: 4AN: 174087Hom.: 0 AF XY: 0.0000155 AC XY: 1AN XY: 64535
GnomAD4 exome AF: 0.00000821 AC: 9AN: 1096237Hom.: 0 Cov.: 31 AF XY: 0.00000552 AC XY: 2AN XY: 362475
GnomAD4 genome ? AF: 0.00000893 AC: 1AN: 112013Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 34189
ClinVar
Submissions by phenotype
Emery-Dreifuss muscular dystrophy Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 03, 2021 | - - |
Emery-Dreifuss muscular dystrophy 1, X-linked Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 02, 2021 | - - |
X-linked Emery-Dreifuss muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 35 of the EMD protein (p.Glu35Lys). This variant is present in population databases (rs794729018, gnomAD 0.01%), 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: 201780). 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 | Jun 26, 2021 | The p.E35K variant (also known as c.103G>A), located in coding exon 2 of the EMD gene, results from a G to A substitution at nucleotide position 103. The glutamic acid at codon 35 is replaced by lysine, an amino acid with similar properties. This alteration has been seen in a healthy exome cohort, but cardiovascular history was not provided (Dharmaraj T et al. Front Cell Dev Biol, 2019 Apr;7:48). Based on data from gnomAD, the A allele has an overall frequency of 0.002% (4/174087) total alleles studied, with 1 hemizygote observed. The highest observed frequency was 0.014% (4/27043) of Latino/Admixed American alleles. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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