rs553354987
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001036.6(RYR3):c.4483A>G(p.Ile1495Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,563,072 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1495F) has been classified as Uncertain significance.
Frequency
Consequence
NM_001036.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.4483A>G | p.Ile1495Val | missense_variant | 34/104 | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.4483A>G | p.Ile1495Val | missense_variant | 34/104 | 1 | NM_001036.6 | P4 | |
RYR3 | ENST00000389232.9 | c.4483A>G | p.Ile1495Val | missense_variant | 34/104 | 5 | A1 | ||
RYR3 | ENST00000415757.7 | c.4483A>G | p.Ile1495Val | missense_variant | 34/103 | 2 | A2 | ||
RYR3 | ENST00000634418.1 | c.4483A>G | p.Ile1495Val | missense_variant | 34/102 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000231 AC: 4AN: 173102Hom.: 0 AF XY: 0.0000217 AC XY: 2AN XY: 92108
GnomAD4 exome AF: 0.0000198 AC: 28AN: 1410894Hom.: 0 Cov.: 32 AF XY: 0.0000172 AC XY: 12AN XY: 696900
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74338
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 20, 2023 | The c.4483A>G (p.I1495V) alteration is located in exon 34 (coding exon 34) of the RYR3 gene. This alteration results from a A to G substitution at nucleotide position 4483, causing the isoleucine (I) at amino acid position 1495 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 461914). This variant has not been reported in the literature in individuals affected with RYR3-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1495 of the RYR3 protein (p.Ile1495Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at