X-154381103-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP3_ModerateBP6BS2
The ENST00000369842.9(EMD):c.671C>T(p.Pro224Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,210,608 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P224R) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000369842.9 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EMD | NM_000117.3 | c.671C>T | p.Pro224Leu | 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.671C>T | p.Pro224Leu | missense_variant | 6/6 | 1 | NM_000117.3 | ENSP00000358857 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000887 AC: 1AN: 112699Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34839
GnomAD3 exomes AF: 0.0000274 AC: 5AN: 182782Hom.: 0 AF XY: 0.0000445 AC XY: 3AN XY: 67482
GnomAD4 exome AF: 0.0000128 AC: 14AN: 1097909Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 6AN XY: 363319
GnomAD4 genome AF: 0.00000887 AC: 1AN: 112699Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34839
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 10, 2020 | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID 201777; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30847666) - |
Uncertain significance, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
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 | Aug 09, 2019 | - - |
X-linked Emery-Dreifuss muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at