Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

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Variant: NM_000540.3(RYR1):c.9093C>T (p.Ala3031=)

CA073137

329085 (ClinVar)

Gene: RYR1

Condition: RYR1-related myopathy

Inheritance Mode: Undetermined mode of inheritance

Link to MONDO

UUID: 87588aa7-9f0a-43ba-a184-8b5de3b15867

Approved on: 2024-08-07

Published on: 2024-10-02

HGVS expressions

NM_000540.3:c.9093C>T

NM_000540.3(RYR1):c.9093C>T (p.Ala3031=)

NC_000019.10:g.38510752C>T

CM000681.2:g.38510752C>T

NC_000019.9:g.39001392C>T

CM000681.1:g.39001392C>T

NC_000019.8:g.43693232C>T

NG_008866.1:g.82053C>T

ENST00000599547.6:c.9093C>T

ENST00000359596.8:c.9093C>T

ENST00000355481.8:c.9093C>T

ENST00000359596.7:c.9093C>T

ENST00000360985.7:c.9090C>T

ENST00000594335.5:c.2545C>T

NM_000540.2:c.9093C>T

NM_001042723.1:c.9093C>T

NM_001042723.2:c.9093C>T

Likely Benign

BS1 BP4 BP7

BA1 PM2

Evidence Links 0

Expert Panel

Congenital Myopathies VCEP

Criteria Specification Information

Criteria Specification: ClinGen Congenital Myopathies Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RYR1 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Congenital Myopathies VCEP

The c.9093C>T (p.Ala3031=) variant (NM_000540.3(RYR1):c.9093C>T (p.Ala3031=)) in RYR1 is a synonymous (silent) variant that is not predicted by Splice AI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by UCSC genome browser (BP4, BP7). The filtering allele frequency (the lower threshold of the 95% CI of 3/6084) of the c.9093C>T variant in RYR1 is 0.0001414 for Middle Eastern chromosomes by gnomAD v4.1, which is higher than the ClinGen Congenital Myopathies VCEP threshold (≥0.0000006) for BS1, and therefore meets this criterion (BS1). In summary, this variant meets the criteria to be classified as likely benign for RYR1-related myopathy, based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: BS1, BP4, BP7 (Congenital Myopathies VCEP Specifications Version 1; 8/7/2024).

BS1

The filtering allele frequency (the lower threshold of the 95% CI of 3/6084) of the c.9093C>T variant in RYR1 is 0.0001414 for Middle Eastern chromosomes by gnomAD v4.1, which is higher than the ClinGen Congenital Myopathies VCEP threshold (≥0.0000006) for BS1, and therefore meets this criterion (BS1).

BP4

The c.9093C>T (p.Ala3031=) variant (NM_000540.3(RYR1):c.9093C>T (p.Ala3031=)) is a synonymous (silent) variant that is not predicted by Splice AI to impact splicing. Splice AI gives a score of 0.00. In addition, it occurs at a nucleotide that is not conserved as shown by UCSC genome browser (BP4, BP7).

BP7

BA1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

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