chr15-33617625-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001036.6(RYR3):​c.2357+4250A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 152,206 control chromosomes in the GnomAD database, including 187 homozygotes. 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 0.029 ( 187 hom., cov: 33)

Consequence

RYR3
NM_001036.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.164
Variant links:
Genes affected
RYR3 (HGNC:10485): (ryanodine receptor 3) The protein encoded by this gene is a ryanodine receptor, which functions to release calcium from intracellular storage for use in many cellular processes. For example, the encoded protein is involved in skeletal muscle contraction by releasing calcium from the sarcoplasmic reticulum followed by depolarization of T-tubules. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0913 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RYR3NM_001036.6 linkuse as main transcriptc.2357+4250A>C intron_variant ENST00000634891.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RYR3ENST00000634891.2 linkuse as main transcriptc.2357+4250A>C intron_variant 1 NM_001036.6 P4Q15413-1
RYR3ENST00000389232.9 linkuse as main transcriptc.2357+4250A>C intron_variant 5 A1
RYR3ENST00000415757.7 linkuse as main transcriptc.2357+4250A>C intron_variant 2 A2Q15413-2
RYR3ENST00000634418.1 linkuse as main transcriptc.2357+4250A>C intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0287
AC:
4366
AN:
152088
Hom.:
182
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0933
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0190
Gnomad ASJ
AF:
0.00778
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000830
Gnomad FIN
AF:
0.0000944
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.00201
Gnomad OTH
AF:
0.0163
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0289
AC:
4393
AN:
152206
Hom.:
187
Cov.:
33
AF XY:
0.0279
AC XY:
2077
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.0937
Gnomad4 AMR
AF:
0.0190
Gnomad4 ASJ
AF:
0.00778
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000623
Gnomad4 FIN
AF:
0.0000944
Gnomad4 NFE
AF:
0.00201
Gnomad4 OTH
AF:
0.0161
Alfa
AF:
0.0140
Hom.:
22
Bravo
AF:
0.0330
Asia WGS
AF:
0.00693
AC:
24
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
5.3
DANN
Benign
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs58822275; hg19: chr15-33909826; API