19-38433746-G-GCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000540.3(RYR1):​c.-81_-80insCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000533 in 375,474 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000053 ( 0 hom. )

Consequence

RYR1
NM_000540.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RYR1NM_000540.3 linkc.-81_-80insCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC 5_prime_UTR_variant Exon 1 of 106 ENST00000359596.8 NP_000531.2 P21817-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RYR1ENST00000359596 linkc.-81_-80insCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC 5_prime_UTR_variant Exon 1 of 106 5 NM_000540.3 ENSP00000352608.2 P21817-1
RYR1ENST00000355481 linkc.-81_-80insCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC 5_prime_UTR_variant Exon 1 of 105 1 ENSP00000347667.3 P21817-2
RYR1ENST00000599547.6 linkn.-84_-83insCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC upstream_gene_variant 2 ENSP00000471601.2 M0R127

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
0.00000533
AC:
2
AN:
375474
Hom.:
0
Cov.:
0
AF XY:
0.00000956
AC XY:
2
AN XY:
209110
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000562
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000493
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-38924386; API