Genetic Variant NM_000540.3:c.-65G>A (chr19-38433765-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000540.3(RYR1):c.-65G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000076 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00025 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RYR1
NM_000540.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.515

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]

RYR1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR1	NM_000540.3 link	c.-65G>A		5_prime_UTR_variant	Exon 1 of 106	ENST00000359596.8	NP_000531.2	P21817-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RYR1	ENST00000359596 link	c.-65G>A	5_prime_UTR_variant	Exon 1 of 106	5	NM_000540.3	ENSP00000352608.2	P21817-1
RYR1	ENST00000355481 link	c.-65G>A	5_prime_UTR_variant	Exon 1 of 105	1		ENSP00000347667.3	P21817-2
RYR1	ENST00000599547.6 link	n.-65G>A	upstream_gene_variant		2		ENSP00000471601.2	M0R127

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

13118

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000249

AC:

AN:

212490

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

119626

show subpopulations

Gnomad4 AFR exome

AF:

0.000395

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000390

Gnomad4 EAS exome

AF:

0.000168

Gnomad4 SAS exome

AF:

0.0000417

Gnomad4 FIN exome

AF:

0.000160

Gnomad4 NFE exome

AF:

0.000327

Gnomad4 OTH exome

AF:

0.000284

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000761

AC:

AN:

13146

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

AN XY:

6922

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00167

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.3

DANN

Benign

0.86

Splicing

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over