rs150028316

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001036.6(RYR3):ā€‹c.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

Scores

3
9
6

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 8.02
Variant links:
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 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
RYR3NM_001036.6 linkuse as main transcriptc.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
RYR3ENST00000634891.2 linkuse as main transcriptc.9950T>C p.Ile3317Thr missense_variant 69/1041 NM_001036.6 ENSP00000489262 P4Q15413-1

Frequencies

GnomAD3 genomes
AF:
0.00169
AC:
258
AN:
152236
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000603
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00807
Gnomad FIN
AF:
0.00179
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00238
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00240
AC:
491
AN:
204946
Hom.:
3
AF XY:
0.00286
AC XY:
313
AN XY:
109386
show subpopulations
Gnomad AFR exome
AF:
0.000486
Gnomad AMR exome
AF:
0.000555
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00829
Gnomad FIN exome
AF:
0.00240
Gnomad NFE exome
AF:
0.00220
Gnomad OTH exome
AF:
0.00245
GnomAD4 exome
AF:
0.00277
AC:
3956
AN:
1427082
Hom.:
16
Cov.:
29
AF XY:
0.00296
AC XY:
2092
AN XY:
706976
show subpopulations
Gnomad4 AFR exome
AF:
0.000335
Gnomad4 AMR exome
AF:
0.000581
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00891
Gnomad4 FIN exome
AF:
0.00242
Gnomad4 NFE exome
AF:
0.00265
Gnomad4 OTH exome
AF:
0.00282
GnomAD4 genome
AF:
0.00169
AC:
258
AN:
152354
Hom.:
0
Cov.:
33
AF XY:
0.00161
AC XY:
120
AN XY:
74516
show subpopulations
Gnomad4 AFR
AF:
0.000601
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00807
Gnomad4 FIN
AF:
0.00179
Gnomad4 NFE
AF:
0.00238
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00203
Hom.:
1
Bravo
AF:
0.00142
TwinsUK
AF:
0.00270
AC:
10
ALSPAC
AF:
0.00208
AC:
8
ESP6500AA
AF:
0.000554
AC:
2
ESP6500EA
AF:
0.00172
AC:
14
ExAC
AF:
0.00201
AC:
242
Asia WGS
AF:
0.00318
AC:
11
AN:
3478

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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2024RYR3: PP3, BS2 -
Epileptic encephalopathy Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 15, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Uncertain
0.010
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.41
T;.;.;.;.
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.94
D;D;D;D;D
M_CAP
Uncertain
0.092
D
MetaRNN
Benign
0.010
T;T;T;T;T
MetaSVM
Uncertain
0.52
D
MutationAssessor
Benign
0.69
N;N;.;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-3.3
.;D;.;.;.
REVEL
Uncertain
0.45
Sift
Benign
0.14
.;T;.;.;.
Polyphen
0.75
P;P;.;.;.
Vest4
0.49
MVP
0.43
MPC
0.29
ClinPred
0.027
T
GERP RS
5.3
Varity_R
0.26
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150028316; hg19: chr15-34094101; API