chr15-33838758-A-G
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_001036.6(RYR3):c.12778A>G(p.Ile4260Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,613,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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_001036.6 missense
Scores
Clinical Significance
Conservation
Publications
- genetic developmental and epileptic encephalopathyInheritance: AD Classification: LIMITED Submitted by: ClinGen, G2P
- congenital myopathyInheritance: AR Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Likely_benign. The variant received -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152166Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000723 AC: 18AN: 249030 AF XY: 0.0000518 show subpopulations
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461680Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 727116 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000171 AC: 26AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74344 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.12778A>G (p.I4260V) alteration is located in exon 89 (coding exon 89) of the RYR3 gene. This alteration results from a A to G substitution at nucleotide position 12778, causing the isoleucine (I) at amino acid position 4260 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Epileptic encephalopathy Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at