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 label mismatch: SGCG vs undefined
  • 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_000231.3(SGCG):c.347G>A (p.Arg116His)

CA145903

92655 (ClinVar)

Gene: SGCG
Condition: autosomal recessive limb-girdle muscular dystrophy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 9218ac95-5e4d-4988-b7e6-c662058c72bd
Approved on: 2025-06-25
Published on: 2025-07-08

HGVS expressions

NM_000231.3:c.347G>A
NM_000231.3(SGCG):c.347G>A (p.Arg116His)
NC_000013.11:g.23250679G>A
CM000675.2:g.23250679G>A
NC_000013.10:g.23824818G>A
CM000675.1:g.23824818G>A
NC_000013.9:g.22722818G>A
NG_008759.1:g.74759G>A
ENST00000218867.4:c.347G>A
ENST00000218867.3:c.347G>A
NM_000231.2:c.347G>A
NM_001378244.1:c.401G>A
NM_001378245.1:c.347G>A
NM_001378246.1:c.347G>A
More

Benign

Met criteria codes 1
BA1
Not Met criteria codes 15
PM6 PM2 PM5 PM3 BS4 BS1 BS2 BP4 BP2 PS1 PS2 PS4 PP3 PP4 PP1

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 SGCG 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_000231.3: c.347G>A variant in SGCG is a missense variant predicted to cause substitution of arginine by histidine at amino acid 116, p.(Arg116His). The filtering allele frequency for this variant is 0.1550 in gnomAD v4.1.0 exomes (the lower threshold of the 95% confidence interval of 944/5768 Middle Eastern chromosomes), which is greater than the LGMD VCEP threshold for BA1, meeting this criterion (BA1). This variant was reported in a single heterozygous state in a patient with sarcoglycanopathy who also had a compound heterozygous pair of variants in SGCA that were considered diagnostic (PMID: 18421900). The REVEL score for this variant is 0.375 and the SpliceAI score is 0.01 (BP4, PP3 not met). 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; 06/25/2025): BA1.
Met criteria codes
BA1
The filtering allele frequency for this variant is 0.1550 in gnomAD v4.1.0 exomes (the lower threshold of the 95% confidence interval of 944/5768 Middle Eastern chromosomes), which is greater than the LGMD VCEP threshold for BA1, meeting this criterion.
Not Met criteria codes
PM6
No patients.
PM2
The allele frequency is higher than the threshold needed to invoke PM2_supporting (>0.00009).
PM5
The other codon (p.Arg116Cys) is a VUS in ClinVar.
PM3
This variant has been observed in a heterozygous state in a patient with an alternative diagnosis (PMID:18421900).
BS4
No affected family members.
BS1
The allele frequency crosses the threshold for BA1 criteria, so BA1 is invoked instead of BS1.
BS2
Not applicable.
BP4
REVEL score is 0.375 (>0.1) and SpliceAI score is 0.01 (<0.05).
BP2
No patients.
PS1
No other variant with the same amino acid change is seen.
PS2
No patients.
PS4
No case-control studies.
PP3
REVEL score is 0.375.
PP4
No patients.
PP1
No affected family members.
Curation History
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