rs772616442
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_000540.3(RYR1):c.3495C>T(p.Gly1165Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000540.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.3495C>T | p.Gly1165Gly | synonymous_variant | Exon 26 of 106 | 5 | NM_000540.3 | ENSP00000352608.2 | ||
RYR1 | ENST00000355481.8 | c.3495C>T | p.Gly1165Gly | synonymous_variant | Exon 26 of 105 | 1 | ENSP00000347667.3 | |||
RYR1 | ENST00000599547.6 | n.3495C>T | non_coding_transcript_exon_variant | Exon 26 of 80 | 2 | ENSP00000471601.2 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251482Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135918
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461876Hom.: 0 Cov.: 34 AF XY: 0.0000413 AC XY: 30AN XY: 727238
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74324
ClinVar
Submissions by phenotype
Malignant hyperthermia, susceptibility to, 1 Uncertain:2
This variant is located in the RYR1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with unspecified RYR1-related disorder (PMID: 30155738) and has not been reported in individuals with malignant hyperthermia susceptibility in the literature. This variant has been identified in 16/282864 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. -
This variant is located in the RYR1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with unspecified RYR1-related disorder (PMID: 30155738) and has not been reported in individuals with malignant hyperthermia susceptibility in the literature. This variant has been identified in 16/282864 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. -
RYR1-related disorder Uncertain:1
This sequence change affects codon 1165 of the RYR1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RYR1 protein. This variant is present in population databases (rs772616442, gnomAD 0.01%). This variant has been observed in individual(s) with RYR1-related disease (PMID: 30155738). ClinVar contains an entry for this variant (Variation ID: 590516). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
not provided Uncertain:1
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Congenital myopathy with fiber type disproportion;C1840365:King Denborough syndrome;C1850674:Congenital multicore myopathy with external ophthalmoplegia;C2930980:Malignant hyperthermia, susceptibility to, 1;C5830701:Central core myopathy Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at