Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000070.3(CAPN3):c.-25G>C

CA618001458

510005 (ClinVar)

Gene: CAPN3
Condition: autosomal recessive limb-girdle muscular dystrophy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 1388f3d4-94ee-46b1-962c-ba17d0b57847
Approved on: 2025-01-07
Published on: 2025-01-07

HGVS expressions

NM_000070.3:c.-25G>C
NM_000070.3(CAPN3):c.-25G>C
NC_000015.10:g.42359781G>C
CM000677.2:g.42359781G>C
NC_000015.9:g.42651979G>C
CM000677.1:g.42651979G>C
NC_000015.8:g.40439271G>C
NG_008660.1:g.16679G>C
ENST00000349748.8:c.-25G>C
ENST00000357568.8:c.-25G>C
ENST00000397163.8:c.-25G>C
ENST00000466369.5:n.540+5328G>C
ENST00000483208.5:n.540+5328G>C
ENST00000495723.1:n.540+5328G>C
ENST00000549793.5:n.540+5328G>C
ENST00000318023.11:c.-25G>C
ENST00000349748.7:c.-25G>C
ENST00000357568.7:c.-25G>C
ENST00000397163.7:c.-25G>C
NM_000070.2:c.-25G>C
NM_024344.1:c.-25G>C
NM_173087.1:c.-25G>C
NM_024344.2:c.-25G>C
NM_173087.2:c.-25G>C
More

Likely Benign

Met criteria codes 2
BP4 BP7
Not Met criteria codes 24
BS2 BS4 BS3 BS1 BP2 BP3 BP1 BP5 PS2 PS4 PS3 PS1 BA1 PP1 PP4 PP3 PP2 PM3 PM1 PM4 PM5 PM6 PM2 PVS1

Evidence Links 0

Expert Panel

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.-25G>C variant is located in the 5’UTR of CAPN3. Because the variant is located in the 5’UTR, it is not expected to alter the amino acid sequence. The c.-25G>C variant is not predicted by SpliceAI to impact splicing (score 0) (BP4, BP7). The highest minor allele frequency of the variant is 0.0001310 for Admixed American genome alleles in gnomAD v3.1.2 (2/15270), which is greater than the LGMD VCEP threshold (<0.0001) for PM2_Supporting (criterion not met). In summary, this variant meets the criteria to be classified as Likely 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; 01/07/2025): BP4, BP7.
Met criteria codes
BP4
The computational splicing predictor SpliceAI gives a score of 0 for both donor and acceptor loss, suggesting that the variant has no impact on splicing since it does not exceed the designated LGMD VCEP threshold (≤0.05) (BP4).
BP7
The c.-25G>C variant is a UTR variant that is not predicted by SpliceAI to impact splicing (score 0). In addition, it occurs at a nucleotide that is not conserved as shown by a PhyloP score of -1.4 (conservation threshold <0.1) (BP4, BP7).
Not Met criteria codes
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The highest minor allele frequency of the variant is 0.0001310 for Admixed American genome alleles in gnomAD v3.1.2 (2/15270), which is greater than the LGMD VCEP threshold (<0.0001) for PM2_Supporting (criterion not met).
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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