rs2572204

Variant names:

• chr15-33503509-A-C
• rs2572204
• NM_001036.6:c.172-122A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-33503509-A-C
• chr15-33503509-A-G
• chr15-33503509-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001036.6(RYR3):​c.172-122A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 4 publications found

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]

RYR3 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen, G2P
• congenital myopathy

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR3	NM_001036.6	c.172-122A>C		intron_variant	Intron 2 of 103	ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2	c.172-122A>C		intron_variant	Intron 2 of 103	1	NM_001036.6	ENSP00000489262.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 469742 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 246718

African (AFR) AF: 0.00 AC: 0 AN: 12812

American (AMR) AF: 0.00 AC: 0 AN: 19236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13994

East Asian (EAS) AF: 0.00 AC: 0 AN: 30452

South Asian (SAS) AF: 0.00 AC: 0 AN: 42488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3572

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 281122

Other (OTH) AF: 0.00 AC: 0 AN: 26136

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 32641

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.70
PhyloP100		-0.013

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

Other links and lift over

dbSNP: rs2572204; hg19: chr15-33795710;