rs1337858544
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PM4_Supporting
The NM_001036.6(RYR3):c.13120_13122delAAG(p.Lys4374del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00000828 in 1,448,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000083 ( 0 hom. )
Consequence
RYR3
NM_001036.6 conservative_inframe_deletion
NM_001036.6 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.27
Publications
0 publications found
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]
RYR3 Gene-Disease associations (from GenCC):
- genetic developmental and epileptic encephalopathyInheritance: AD Classification: LIMITED Submitted by: ClinGen, G2P
- congenital myopathyInheritance: AR Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_001036.6. Strenght limited to Supporting due to length of the change: 1aa.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001036.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RYR3 | NM_001036.6 | MANE Select | c.13120_13122delAAG | p.Lys4374del | conservative_inframe_deletion | Exon 91 of 104 | NP_001027.3 | ||
| RYR3 | NM_001243996.4 | c.13105_13107delAAG | p.Lys4369del | conservative_inframe_deletion | Exon 90 of 103 | NP_001230925.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RYR3 | ENST00000634891.2 | TSL:1 MANE Select | c.13120_13122delAAG | p.Lys4374del | conservative_inframe_deletion | Exon 91 of 104 | ENSP00000489262.1 | ||
| RYR3 | ENST00000389232.9 | TSL:5 | c.13117_13119delAAG | p.Lys4373del | conservative_inframe_deletion | Exon 91 of 104 | ENSP00000373884.5 | ||
| RYR3 | ENST00000415757.7 | TSL:2 | c.13105_13107delAAG | p.Lys4369del | conservative_inframe_deletion | Exon 90 of 103 | ENSP00000399610.3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000878 AC: 2AN: 227724 AF XY: 0.0000163 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
227724
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000828 AC: 12AN: 1448734Hom.: 0 AF XY: 0.0000111 AC XY: 8AN XY: 719124 show subpopulations
GnomAD4 exome
AF:
AC:
12
AN:
1448734
Hom.:
AF XY:
AC XY:
8
AN XY:
719124
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33260
American (AMR)
AF:
AC:
0
AN:
42844
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25766
East Asian (EAS)
AF:
AC:
1
AN:
39374
South Asian (SAS)
AF:
AC:
1
AN:
83502
European-Finnish (FIN)
AF:
AC:
0
AN:
52560
Middle Eastern (MID)
AF:
AC:
0
AN:
5730
European-Non Finnish (NFE)
AF:
AC:
8
AN:
1105756
Other (OTH)
AF:
AC:
2
AN:
59942
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Epileptic encephalopathy (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
Publications
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