rs377437662
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001036.6(RYR3):c.9831-8G>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,606,954 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001036.6 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.9831-8G>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.9831-8G>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001036.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000875 AC: 133AN: 152016Hom.: 2 Cov.: 33
GnomAD3 exomes AF: 0.000225 AC: 56AN: 249008Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135092
GnomAD4 exome AF: 0.000105 AC: 153AN: 1454820Hom.: 1 Cov.: 28 AF XY: 0.0000925 AC XY: 67AN XY: 724362
GnomAD4 genome AF: 0.000887 AC: 135AN: 152134Hom.: 2 Cov.: 33 AF XY: 0.000686 AC XY: 51AN XY: 74388
ClinVar
Submissions by phenotype
Epileptic encephalopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 03, 2023 | - - |
RYR3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 14, 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at