rs150028316
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001036.6(RYR3):āc.9950T>Cā(p.Ile3317Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,579,436 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0017 ( 0 hom., cov: 33)
Exomes š: 0.0028 ( 16 hom. )
Consequence
RYR3
NM_001036.6 missense
NM_001036.6 missense
Scores
3
9
6
Clinical Significance
Conservation
PhyloP100: 8.02
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 Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.010166019).
BP6
Variant 15-33801900-T-C is Benign according to our data. Variant chr15-33801900-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 461994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-33801900-T-C is described in Lovd as [Likely_benign].
BS2
High Homozygotes in GnomAdExome4 at 16 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.9950T>C | p.Ile3317Thr | missense_variant | 69/104 | ENST00000634891.2 | NP_001027.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.9950T>C | p.Ile3317Thr | missense_variant | 69/104 | 1 | NM_001036.6 | ENSP00000489262 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00169 AC: 258AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00240 AC: 491AN: 204946Hom.: 3 AF XY: 0.00286 AC XY: 313AN XY: 109386
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GnomAD4 exome AF: 0.00277 AC: 3956AN: 1427082Hom.: 16 Cov.: 29 AF XY: 0.00296 AC XY: 2092AN XY: 706976
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GnomAD4 genome AF: 0.00169 AC: 258AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.00161 AC XY: 120AN XY: 74516
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | RYR3: PP3, BS2 - |
Epileptic encephalopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 15, 2024 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;N;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
.;D;.;.;.
REVEL
Uncertain
Sift
Benign
.;T;.;.;.
Polyphen
P;P;.;.;.
Vest4
MVP
0.43
MPC
0.29
ClinPred
T
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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