rs376790408
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4BP6
The NM_000540.3(RYR1):c.9896G>T(p.Gly3299Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.9896G>T | p.Gly3299Val | missense_variant | 66/106 | ENST00000359596.8 | NP_000531.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.9896G>T | p.Gly3299Val | missense_variant | 66/106 | 5 | NM_000540.3 | ENSP00000352608.2 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152140Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000604 AC: 15AN: 248252Hom.: 0 AF XY: 0.0000372 AC XY: 5AN XY: 134504
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461614Hom.: 0 Cov.: 34 AF XY: 0.0000151 AC XY: 11AN XY: 727124
GnomAD4 genome AF: 0.000177 AC: 27AN: 152258Hom.: 0 Cov.: 31 AF XY: 0.000134 AC XY: 10AN XY: 74430
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 08, 2022 | The c.9896G>T (p.G3299V) alteration is located in exon 66 (coding exon 66) of the RYR1 gene. This alteration results from a G to T substitution at nucleotide position 9896, causing the glycine (G) at amino acid position 3299 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 24, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Malignant hyperthermia, susceptibility to, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
RYR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 17, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at