chr19-38433746-G-GC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000540.3(RYR1):​c.-81dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0031 ( 2 hom. )
Failed GnomAD Quality Control

Consequence

RYR1
NM_000540.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:4

Conservation

PhyloP100: 2.43
Variant links:
Genes affected
RYR1 (HGNC:10483): (ryanodine receptor 1) This gene encodes a ryanodine receptor found in skeletal muscle. The encoded protein functions as a calcium release channel in the sarcoplasmic reticulum but also serves to connect the sarcoplasmic reticulum and transverse tubule. Mutations in this gene are associated with malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. Alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RYR1NM_000540.3 linkuse as main transcriptc.-81dup 5_prime_UTR_variant 1/106 ENST00000359596.8 NP_000531.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RYR1ENST00000359596.8 linkuse as main transcriptc.-81dup 5_prime_UTR_variant 1/1065 NM_000540.3 ENSP00000352608 A2P21817-1
RYR1ENST00000355481.8 linkuse as main transcriptc.-81dup 5_prime_UTR_variant 1/1051 ENSP00000347667 P4P21817-2

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
3
AN:
145246
Hom.:
0
Cov.:
30
FAILED QC
Gnomad AFR
AF:
0.0000257
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000104
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000151
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00308
AC:
1155
AN:
374914
Hom.:
2
Cov.:
0
AF XY:
0.00286
AC XY:
598
AN XY:
208814
show subpopulations
Gnomad4 AFR exome
AF:
0.00628
Gnomad4 AMR exome
AF:
0.0131
Gnomad4 ASJ exome
AF:
0.00660
Gnomad4 EAS exome
AF:
0.000507
Gnomad4 SAS exome
AF:
0.00325
Gnomad4 FIN exome
AF:
0.00107
Gnomad4 NFE exome
AF:
0.00172
Gnomad4 OTH exome
AF:
0.00233
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000207
AC:
3
AN:
145246
Hom.:
0
Cov.:
30
AF XY:
0.0000141
AC XY:
1
AN XY:
70886
show subpopulations
Gnomad4 AFR
AF:
0.0000257
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000104
Gnomad4 NFE
AF:
0.0000151
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Central core myopathy Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Malignant hyperthermia of anesthesia Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Multiminicore myopathy Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Neuromuscular disease, congenital, with uniform type 1 fiber Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs886054374; hg19: chr19-38924386; API