NM_000540.3:c.12861_12869delCACGGCGGC
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3BP6BS1
The NM_000540.3(RYR1):c.12861_12869delCACGGCGGC(p.Thr4288_Ala4290del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00062 in 1,117,954 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000540.3 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
Publications
- malignant hyperthermia, susceptibility to, 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, Ambry Genetics
- congenital multicore myopathy with external ophthalmoplegiaInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp
- RYR1-related myopathyInheritance: AR, AD Classification: DEFINITIVE Submitted by: ClinGen
- central core myopathyInheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
- King-Denborough syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- malignant hyperthermia of anesthesiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- autosomal recessive centronuclear myopathyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- benign Samaritan congenital myopathyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- congenital myopathy with myasthenic-like onsetInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- lethal multiple pterygium syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Likely_benign. The variant received -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00270 AC: 398AN: 147512Hom.: 1 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.000391 AC: 1AN: 2558 AF XY: 0.000567 show subpopulations
GnomAD4 exome AF: 0.000302 AC: 293AN: 970336Hom.: 1 AF XY: 0.000302 AC XY: 138AN XY: 456652 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00271 AC: 400AN: 147618Hom.: 1 Cov.: 32 AF XY: 0.00278 AC XY: 200AN XY: 71954 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
- -
RYR1: PM4, BS2 -
King Denborough syndrome;C1850674:Congenital multicore myopathy with external ophthalmoplegia;C2930980:Malignant hyperthermia, susceptibility to, 1;C5830701:Central core myopathy Uncertain:1
- -
RYR1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at