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_000231.3(SGCG):c.525del (p.Phe175fs)

CA346837

189243 (ClinVar)

Gene: SGCG
Condition: autosomal recessive limb-girdle muscular dystrophy
Inheritance Mode: Autosomal recessive inheritance
UUID: 4503b450-84a7-485a-b082-22222ddf43a9
Approved on: 2025-01-08
Published on: 2025-01-08

HGVS expressions

NM_000231.3:c.525del
NM_000231.3(SGCG):c.525del (p.Phe175fs)
NC_000013.11:g.23295434del
CM000675.2:g.23295434del
NC_000013.10:g.23869573del
CM000675.1:g.23869573del
NC_000013.9:g.22767573del
NG_008759.1:g.119514del
ENST00000683210.1:c.2186-6187del
ENST00000218867.4:c.525del
ENST00000218867.3:c.525del
NM_000231.2:c.525del
NM_001378244.1:c.579del
NM_001378245.1:c.525del
NM_001378246.1:c.525del
More

Likely Pathogenic

Met criteria codes 4
PVS1_Strong PP1_Moderate PP4 PM3
Not Met criteria codes 22
PS1 PS2 PS3 PS4 BP5 BP7 BP4 BP3 BP1 BP2 PP2 PP3 PM6 PM2 PM1 PM5 PM4 BA1 BS1 BS4 BS3 BS2

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.525del p.(Phe175LeufsTer20) variant in SGCG is a frameshift variant that is predicted to introduce a premature stop codon. The resulting transcript is predicted to escape nonsense mediated decay but truncate >10% of the protein (PVS1_Strong). This variant has been detected in at least five apparently unrelated patients with autosomal recessive limb girdle muscular dystrophy, including in a homozygous state in at least four individuals (1.0 pt, PMID: 16616845, 10993494, 18285821, 10942431; ClinVar SCV001164546.1) (PM3). At least one patient with this variant displayed progressive limb girdle muscle weakness (PP4). While absent gamma-sarcoglycan protein expression has been reported in the skeletal muscle of patients with this variant, detection may be dependent on the antibody used due to the production of a truncated protein (PMID: 10993494, 16616845, 10942431). The variant has been reported to segregate with autosomal recessive LGMD in four affected family members from two families (PP1_Moderate; PMID: 10942431, ClinVar SCV001164546.1). The highest minor allele frequency of this variant is 0.0002619 (4/15274 genome chromosomes) in the Admixed American population in gnomAD v3.2.1, which is greater than the VCEP threshold (0.00009) for PM2_Supporting (criterion not met). In summary, this variant meets the criteria to be classified as Likely Pathogenic 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; 01/08/2025): PVS1_Strong, PM3, PP4, PP1_Moderate.
Met criteria codes
PVS1_Strong
The NM_000231.3: c.525del p.(Phe175LeufsTer20) variant in SGCG is a frameshift variant that is predicted to introduce a premature stop codon. The resulting transcript is predicted to escape nonsense mediated decay but truncate >10% of the protein (PVS1_Strong).
PP1_Moderate
The variant has been reported to segregate with autosomal recessive LGMD in four affected family members from two families (PP1_Moderate; PMID: 10942431, SCV001164546.1).
PP4
At least one patient with this variant displayed progressive muscle weakness. While absent gamma-sarcoglycan protein expression has been reported in the skeletal muscle of patients with this variant, detection may be dependent on the antibody used (PP4; PMID: 10993494, 16616845, 10942431).
PM3
This variant has been detected in at least five patients with autosomal recessive limb girdle muscular dystrophy, including in a homozygous state in at least four individuals (1.0 pt, PMID: 16616845, 10993494, 18285821, 10942431; SCV001164546.1) (PM3).
Not Met criteria codes
PS1
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
PS3
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
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
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
BP2
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
PP3
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 this variant is 0.0002619 (4/15274 genome chromosomes) in the Admixed American population in gnomAD v3.2.1, which is greater than the ClinGen LGMD threshold (0.00009) for PM2_Supporting (criterion not met).
PM1
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
PM4
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
BS1
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
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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