rs149096607
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP2PP3
The NM_000540.3(RYR1):āc.3311C>Gā(p.Ala1104Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,870 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 Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1104V) 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 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.3311C>G | p.Ala1104Gly | missense_variant | 25/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.3311C>G | p.Ala1104Gly | missense_variant | 25/106 | 5 | NM_000540.3 | A2 | |
RYR1 | ENST00000355481.8 | c.3311C>G | p.Ala1104Gly | missense_variant | 25/105 | 1 | P4 | ||
RYR1 | ENST00000594111.1 | n.404C>G | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
RYR1 | ENST00000599547.6 | c.3311C>G | p.Ala1104Gly | missense_variant, NMD_transcript_variant | 25/80 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461870Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727240
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2020 | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at