rs148515772
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_000117.3(EMD):c.470G>A(p.Arg157Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000388 in 1,210,229 control chromosomes in the GnomAD database, including 1 homozygotes. There are 15 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000117.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EMD | NM_000117.3 | c.470G>A | p.Arg157Gln | missense_variant | 6/6 | ENST00000369842.9 | NP_000108.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EMD | ENST00000369842.9 | c.470G>A | p.Arg157Gln | missense_variant | 6/6 | 1 | NM_000117.3 | ENSP00000358857.4 |
Frequencies
GnomAD3 genomes AF: 0.0000802 AC: 9AN: 112222Hom.: 0 Cov.: 24 AF XY: 0.000116 AC XY: 4AN XY: 34406
GnomAD3 exomes AF: 0.0000820 AC: 15AN: 183002Hom.: 0 AF XY: 0.0000739 AC XY: 5AN XY: 67638
GnomAD4 exome AF: 0.0000346 AC: 38AN: 1098007Hom.: 1 Cov.: 32 AF XY: 0.0000303 AC XY: 11AN XY: 363421
GnomAD4 genome AF: 0.0000802 AC: 9AN: 112222Hom.: 0 Cov.: 24 AF XY: 0.000116 AC XY: 4AN XY: 34406
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 06, 2023 | Variant summary: EMD c.470G>A (p.Arg157Gln) results in a conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.2e-05 in 183002 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in EMD causing Cardiomyopathy (8.2e-05 vs 0.0071), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.470G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Emery-Dreifuss muscular dystrophy 1, X-linked Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 17, 2023 | - - |
X-linked Emery-Dreifuss muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at