19-38444710-TC-TCCC

Position:

• chr19-38444710-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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767

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.631+38_631+39dupCC		intron_variant		ENST00000359596.8	NP_000531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR1	ENST00000359596.8	c.631+33_631+34insCC		intron_variant		5	NM_000540.3	ENSP00000352608.2
RYR1	ENST00000355481.8	c.631+33_631+34insCC		intron_variant		1		ENSP00000347667.3
RYR1	ENST00000599547.6	n.631+33_631+34insCC		intron_variant		2		ENSP00000471601.2

Frequencies

GnomAD3 genomes AF: 0.000282 AC: 42 AN: 148680 Hom.: 0 Cov.: 0

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

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

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

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35018208; hg19: chr19-38935350;