19-38580447-C-T
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_000540.3(RYR1):c.14589C>T(p.Phe4863Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00624 in 1,614,160 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000540.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00591 AC: 899AN: 152162Hom.: 11 Cov.: 31
GnomAD3 exomes AF: 0.00609 AC: 1531AN: 251478Hom.: 10 AF XY: 0.00611 AC XY: 831AN XY: 135912
GnomAD4 exome AF: 0.00628 AC: 9181AN: 1461878Hom.: 52 Cov.: 34 AF XY: 0.00606 AC XY: 4410AN XY: 727240
GnomAD4 genome AF: 0.00590 AC: 899AN: 152282Hom.: 11 Cov.: 31 AF XY: 0.00721 AC XY: 537AN XY: 74434
ClinVar
Submissions by phenotype
not specified Benign:6
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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Malignant hyperthermia, susceptibility to, 1 Benign:3
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
not provided Benign:2
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RYR1: BP4, BS2 -
Congenital multicore myopathy with external ophthalmoplegia Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
RYR1-related disorder Benign:1
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Neuromuscular disease, congenital, with uniform type 1 fiber Benign: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 Benign:1
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Central core myopathy Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at