chr19-38451827-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP2PP3_ModeratePP5_Moderate
The NM_000540.3(RYR1):c.1186G>A(p.Glu396Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E396S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000540.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.1186G>A | p.Glu396Lys | missense_variant | 12/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.1186G>A | p.Glu396Lys | missense_variant | 12/106 | 5 | NM_000540.3 | A2 | |
RYR1 | ENST00000355481.8 | c.1186G>A | p.Glu396Lys | missense_variant | 12/105 | 1 | P4 | ||
RYR1 | ENST00000599547.6 | c.1186G>A | p.Glu396Lys | missense_variant, NMD_transcript_variant | 12/80 | 2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727246
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Myopathy;C0035229:Respiratory insufficiency;C0699743:Congenital muscular dystrophy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | May 21, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at