rs921083301
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000540.3(RYR1):c.12966G>A(p.Arg4322=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000371 in 1,077,154 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00010 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
RYR1
NM_000540.3 synonymous
NM_000540.3 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 0.613
Genes affected
RYR1 (HGNC:10483): (ryanodine receptor 1) This gene encodes a ryanodine receptor found in skeletal muscle. The encoded protein functions as a calcium release channel in the sarcoplasmic reticulum but also serves to connect the sarcoplasmic reticulum and transverse tubule. Mutations in this gene are associated with malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. Alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
Variant 19-38565300-G-A is Benign according to our data. Variant chr19-38565300-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 590420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.613 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.12966G>A | p.Arg4322= | synonymous_variant | 91/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.12966G>A | p.Arg4322= | synonymous_variant | 91/106 | 5 | NM_000540.3 | A2 | |
RYR1 | ENST00000355481.8 | c.12951G>A | p.Arg4317= | synonymous_variant | 90/105 | 1 | P4 | ||
RYR1 | ENST00000689936.1 | c.1359G>A | p.Arg453= | synonymous_variant | 8/22 | ||||
RYR1 | ENST00000688602.1 | c.1377G>A | p.Arg459= | synonymous_variant, NMD_transcript_variant | 9/23 |
Frequencies
GnomAD3 genomes ? AF: 0.000102 AC: 15AN: 147066Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000269 AC: 25AN: 930088Hom.: 0 Cov.: 30 AF XY: 0.0000344 AC XY: 15AN XY: 435596
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GnomAD4 genome ? AF: 0.000102 AC: 15AN: 147066Hom.: 0 Cov.: 32 AF XY: 0.000126 AC XY: 9AN XY: 71550
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
RYR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 18, 2017 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at