rs1009308978
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001036.6(RYR3):c.5242C>T(p.Leu1748Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001036.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.5242C>T | p.Leu1748Phe | missense_variant | 35/104 | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.5242C>T | p.Leu1748Phe | missense_variant | 35/104 | 1 | NM_001036.6 | P4 | |
RYR3 | ENST00000389232.9 | c.5242C>T | p.Leu1748Phe | missense_variant | 35/104 | 5 | A1 | ||
RYR3 | ENST00000415757.7 | c.5242C>T | p.Leu1748Phe | missense_variant | 35/103 | 2 | A2 | ||
RYR3 | ENST00000634418.1 | c.5242C>T | p.Leu1748Phe | missense_variant | 35/102 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249362Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135288
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461776Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 727168
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 15, 2017 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a RYR3-related disease. This sequence change replaces leucine with phenylalanine at codon 1748 of the RYR3 protein (p.Leu1748Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at