rs182972491
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The ENST00000634891.2(RYR3):c.9799C>T(p.Pro3267Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00021 ( 0 hom. )
Consequence
RYR3
ENST00000634891.2 missense
ENST00000634891.2 missense
Scores
10
6
2
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
RYR3 (HGNC:10485): (ryanodine receptor 3) The protein encoded by this gene is a ryanodine receptor, which functions to release calcium from intracellular storage for use in many cellular processes. For example, the encoded protein is involved in skeletal muscle contraction by releasing calcium from the sarcoplasmic reticulum followed by depolarization of T-tubules. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 15-33788427-C-T is Benign according to our data. Variant chr15-33788427-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 461990.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1, not_provided=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.9799C>T | p.Pro3267Ser | missense_variant | 67/104 | ENST00000634891.2 | NP_001027.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.9799C>T | p.Pro3267Ser | missense_variant | 67/104 | 1 | NM_001036.6 | ENSP00000489262 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000276 AC: 42AN: 152176Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000313 AC: 78AN: 248888Hom.: 0 AF XY: 0.000274 AC XY: 37AN XY: 135072
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GnomAD4 exome AF: 0.000209 AC: 306AN: 1461596Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 147AN XY: 727080
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GnomAD4 genome AF: 0.000276 AC: 42AN: 152294Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74466
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1Other:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 05, 2017 | - - |
Epileptic encephalopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 06, 2022 | - - |
not provided Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | Variant interpretted as Uncertain significance and reported on 08-01-2017 by Lab or GTR ID 61756. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Pathogenic
D;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
.;D;.;.;.
REVEL
Uncertain
Sift
Uncertain
.;D;.;.;.
Polyphen
D;D;.;.;.
Vest4
MVP
0.61
MPC
0.74
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at