rs201914506
Positions:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_001036.6(RYR3):āc.8236A>Gā(p.Ile2746Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000301 in 1,612,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00037 ( 0 hom., cov: 32)
Exomes š: 0.00029 ( 0 hom. )
Consequence
RYR3
NM_001036.6 missense
NM_001036.6 missense
Scores
2
5
8
Clinical Significance
Conservation
PhyloP100: 9.32
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.086467475).
BP6
?
Variant 15-33750015-A-G is Benign according to our data. Variant chr15-33750015-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 530977.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.8236A>G | p.Ile2746Val | missense_variant | 56/104 | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.8236A>G | p.Ile2746Val | missense_variant | 56/104 | 1 | NM_001036.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000368 AC: 56AN: 152104Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
56
AN:
152104
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000328 AC: 81AN: 246752Hom.: 0 AF XY: 0.000337 AC XY: 45AN XY: 133688
GnomAD3 exomes
AF:
AC:
81
AN:
246752
Hom.:
AF XY:
AC XY:
45
AN XY:
133688
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000294 AC: 429AN: 1460404Hom.: 0 Cov.: 31 AF XY: 0.000289 AC XY: 210AN XY: 726264
GnomAD4 exome
AF:
AC:
429
AN:
1460404
Hom.:
Cov.:
31
AF XY:
AC XY:
210
AN XY:
726264
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000368 AC: 56AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27AN XY: 74302
GnomAD4 genome
?
AF:
AC:
56
AN:
152104
Hom.:
Cov.:
32
AF XY:
AC XY:
27
AN XY:
74302
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
0
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
?
AF:
AC:
45
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 04, 2022 | The c.8236A>G (p.I2746V) alteration is located in exon 56 (coding exon 56) of the RYR3 gene. This alteration results from a A to G substitution at nucleotide position 8236, causing the isoleucine (I) at amino acid position 2746 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2022 | - - |
Epileptic encephalopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 28, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Pathogenic
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
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Polyphen
B;B;.;.;.
Vest4
MVP
0.46
MPC
0.23
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at