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]

Variant: NM_000070.3(CAPN3):c.1537-48T>C

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA145717

92406 (ClinVar)

Gene: CAPN3

Condition: autosomal recessive limb-girdle muscular dystrophy

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 7c537da7-3355-4fc6-a976-1276903ec495

Approved on: 2025-03-14

Published on: 2025-04-04

HGVS expressions

NM_000070.3:c.1537-48T>C

NM_000070.3(CAPN3):c.1537-48T>C

NC_000015.10:g.42402746T>C

CM000677.2:g.42402746T>C

NC_000015.9:g.42694944T>C

CM000677.1:g.42694944T>C

NC_000015.8:g.40482236T>C

NG_008660.1:g.59644T>C

ENST00000349748.8:c.1393-48T>C

ENST00000357568.8:c.1537-48T>C

ENST00000397163.8:c.1537-48T>C

ENST00000466369.5:n.2046-48T>C

ENST00000483208.5:n.2378T>C

ENST00000495723.1:n.2378T>C

ENST00000549793.5:n.1768-48T>C

ENST00000638141.2:n.1408-48T>C

ENST00000673705.1:c.309+3094T>C

ENST00000673813.1:n.459-48T>C

ENST00000318023.11:c.1393-48T>C

ENST00000349748.7:c.1393-48T>C

ENST00000357568.7:c.1537-48T>C

ENST00000397163.7:c.1537-48T>C

ENST00000397200.8:c.1-48T>C

ENST00000569827.5:c.1-48T>C

NM_000070.2:c.1537-48T>C

NM_024344.1:c.1537-48T>C

NM_173087.1:c.1393-48T>C

NM_173088.1:c.1-48T>C

NM_024344.2:c.1537-48T>C

NM_173087.2:c.1393-48T>C

NM_173088.2:c.1-48T>C

Benign

BP7 BP4 BA1

Evidence Links 0

Expert Panel

Limb Girdle Muscular Dystrophy VCEP

Criteria Specification Information

Criteria Specification: ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CAPN3 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Limb Girdle Muscular Dystrophy VCEP

The NM_000070.3: c.1537-48T>C variant in CAPN3 is an intronic variant. The filtering allele frequency for this variant is 0.9344 in gnomAD v4.1.0 (the lower threshold of the 95% CI of 31266/33150 African/African American exome chromosomes), which is greater than the ClinGen LGMD VCEP threshold ≥0.003 for BA1 (BA1). The SpliceAI prediction of 0.00 indicates no splicing impact and does not exceed the LGMD VCEP threshold of ≤0.05 (BP4). This variant is also not in a splice region (BP7). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 1.0.0; 03/14/2025): BA1, BP4, BP7.

BP7

This intronic variant is not located in a splice region and is not predicted to impact splicing by SpliceAI (BP7).

BP4

The SpliceAI database value of 0.00 indicates no splicing impact since it does not exceed the the LGMD VCEP threshold of < 0.05 (BP4). Additionally, the Variant Effect Predictor (VEP) database indicates a clinical significance of 'benign' for this variant. Multiple lines of computational evidence suggest no impact on gene or gene product as designated by the LGMD VCEP criterion for BP4.

BA1

The filtering allele frequency for this variant is 0.9344 in gnomAD v4.1.0 (the lower threshold of the 95% CI of 31266/33150 African/African American exome chromosomes), which is greater than the ClinGen LGMD VCEP threshold >0.003 for BA1 and therefore meets this criterion (BA1).

Curation History

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