rs772652844
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_000540.3(RYR1):c.447G>A(p.Met149Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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_000540.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.447G>A | p.Met149Ile | missense_variant | Exon 6 of 106 | 5 | NM_000540.3 | ENSP00000352608.2 | ||
RYR1 | ENST00000355481.8 | c.447G>A | p.Met149Ile | missense_variant | Exon 6 of 105 | 1 | ENSP00000347667.3 | |||
RYR1 | ENST00000599547.6 | n.447G>A | non_coding_transcript_exon_variant | Exon 6 of 80 | 2 | ENSP00000471601.2 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152090Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000955 AC: 24AN: 251404Hom.: 0 AF XY: 0.000132 AC XY: 18AN XY: 135880
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461736Hom.: 0 Cov.: 32 AF XY: 0.0000468 AC XY: 34AN XY: 727178
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152090Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74288
ClinVar
Submissions by phenotype
not provided Uncertain:2
RYR1: PM2, BP4 -
- -
RYR1-related disorder Benign:1
- -
Malignant hyperthermia, susceptibility to, 1 Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at