19-38565378-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_000540.3(RYR1):c.13044G>A(p.Ala4348=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000894 in 1,341,766 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A4348A) has been classified as Likely benign.
Frequency
Consequence
NM_000540.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.13044G>A | p.Ala4348= | synonymous_variant | 91/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.13044G>A | p.Ala4348= | synonymous_variant | 91/106 | 5 | NM_000540.3 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000199 AC: 3AN: 150444Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000755 AC: 9AN: 1191322Hom.: 0 Cov.: 31 AF XY: 0.00000860 AC XY: 5AN XY: 581174
GnomAD4 genome AF: 0.0000199 AC: 3AN: 150444Hom.: 0 Cov.: 32 AF XY: 0.0000272 AC XY: 2AN XY: 73416
ClinVar
Submissions by phenotype
RYR1-related disorder Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 21, 2019 | 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). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 02, 2014 | - - |
Congenital myopathy with fiber type disproportion;C0751951:Central core myopathy;C1840365:King Denborough syndrome;C1850674:Congenital multicore myopathy with external ophthalmoplegia;C2930980:Malignant hyperthermia, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 29, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at