chr15-33859650-G-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BP4_ModerateBP6_Moderate
The NM_001036.6(RYR3):c.14218G>C(p.Asp4740His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,613,854 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 2 hom. )
Consequence
RYR3
NM_001036.6 missense
NM_001036.6 missense
Scores
10
2
3
Clinical Significance
Conservation
PhyloP100: 9.90
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 Likely_benign. Variant got -3 ACMG points.
PP3
?
Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Eigen, M_CAP, phyloP100way_vertebrate, PrimateAI, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationAssessor, MutationTaster was below the threshold]
BP4
?
Computational evidence support a benign effect (MetaRNN=0.08045742).
BP6
?
Variant 15-33859650-G-C is Benign according to our data. Variant chr15-33859650-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 732264.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.14218G>C | p.Asp4740His | missense_variant | 100/104 | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.14218G>C | p.Asp4740His | missense_variant | 100/104 | 1 | NM_001036.6 | P4 | |
ENST00000560268.2 | n.70-556C>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000477 AC: 119AN: 249220Hom.: 0 AF XY: 0.000636 AC XY: 86AN XY: 135206
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GnomAD4 exome AF: 0.000241 AC: 352AN: 1461660Hom.: 2 Cov.: 31 AF XY: 0.000358 AC XY: 260AN XY: 727108
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GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74354
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 24, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Pathogenic
D;.;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Benign
M;.;.;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Polyphen
D;D;.;.;.;.
Vest4
MutPred
Gain of sheet (P = 0.0344);.;.;.;.;.;
MVP
0.98
MPC
1.9
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