rs201524472
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate
The NM_001036.6(RYR3):āc.5524A>Cā(p.Lys1842Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000186 in 1,613,360 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.00014 ( 0 hom., cov: 32)
Exomes š: 0.00019 ( 0 hom. )
Consequence
RYR3
NM_001036.6 missense
NM_001036.6 missense
Scores
2
7
6
Clinical Significance
Conservation
PhyloP100: 5.16
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 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 15-33663642-A-C is Benign according to our data. Variant chr15-33663642-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 461930.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.5524A>C | p.Lys1842Gln | missense_variant | 36/104 | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.5524A>C | p.Lys1842Gln | missense_variant | 36/104 | 1 | NM_001036.6 | P4 | |
RYR3 | ENST00000389232.9 | c.5524A>C | p.Lys1842Gln | missense_variant | 36/104 | 5 | A1 | ||
RYR3 | ENST00000415757.7 | c.5524A>C | p.Lys1842Gln | missense_variant | 36/103 | 2 | A2 | ||
RYR3 | ENST00000634418.1 | c.5524A>C | p.Lys1842Gln | missense_variant | 36/102 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000190 AC: 47AN: 247970Hom.: 0 AF XY: 0.000201 AC XY: 27AN XY: 134504
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GnomAD4 exome AF: 0.000191 AC: 279AN: 1461066Hom.: 0 Cov.: 31 AF XY: 0.000183 AC XY: 133AN XY: 726716
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GnomAD4 genome AF: 0.000138 AC: 21AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74470
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Epileptic encephalopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 16, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Polyphen
D;P;.;.;.
Vest4
MVP
0.72
MPC
0.24
ClinPred
T
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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