chr19-38433746-G-GC

Position:

• 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:4
• Conservation: PhyloP100: 2.43

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR1	NM_000540.3	c.-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
RYR1	ENST00000359596.8	c.-81dup		5_prime_UTR_variant	1/106	5	NM_000540.3	ENSP00000352608	A2
RYR1	ENST00000355481.8	c.-81dup		5_prime_UTR_variant	1/105	1		ENSP00000347667	P4

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

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

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

Submissions by phenotype

Central core myopathy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Malignant hyperthermia of anesthesia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Multiminicore myopathy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Neuromuscular disease, congenital, with uniform type 1 fiber Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886054374; hg19: chr19-38924386;