19-38444710-TC-TCCC

Variant summary

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

The NM_000540.3(RYR1):​c.631+38_631+39dupCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,474,990 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: 𝑓 0.00028 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.767
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 linkc.631+38_631+39dupCC intron_variant ENST00000359596.8 NP_000531.2 P21817-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RYR1ENST00000359596.8 linkc.631+33_631+34insCC intron_variant 5 NM_000540.3 ENSP00000352608.2 P21817-1
RYR1ENST00000355481.8 linkc.631+33_631+34insCC intron_variant 1 ENSP00000347667.3 P21817-2
RYR1ENST00000599547.6 linkn.631+33_631+34insCC intron_variant 2 ENSP00000471601.2 M0R127

Frequencies

GnomAD3 genomes
AF:
0.000282
AC:
42
AN:
148680
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.000300
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000445
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000141
AC:
30
AN:
213030
Hom.:
0
AF XY:
0.0000781
AC XY:
9
AN XY:
115266
show subpopulations
Gnomad AFR exome
AF:
0.0000757
Gnomad AMR exome
AF:
0.0000653
Gnomad ASJ exome
AF:
0.000106
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000270
Gnomad OTH exome
AF:
0.000185
GnomAD4 exome
AF:
0.000237
AC:
314
AN:
1326194
Hom.:
0
Cov.:
21
AF XY:
0.000250
AC XY:
166
AN XY:
664092
show subpopulations
Gnomad4 AFR exome
AF:
0.000129
Gnomad4 AMR exome
AF:
0.0000726
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000192
Gnomad4 NFE exome
AF:
0.000296
Gnomad4 OTH exome
AF:
0.000197
GnomAD4 genome
AF:
0.000282
AC:
42
AN:
148796
Hom.:
0
Cov.:
0
AF XY:
0.000152
AC XY:
11
AN XY:
72350
show subpopulations
Gnomad4 AFR
AF:
0.000299
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000445
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000236
Hom.:
2967

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

LitVar

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

Other links and lift over

dbSNP: rs35018208; hg19: chr19-38935350; API