13-23295441-TC-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000231.3(SGCG):c.533delC(p.Ser178fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000231.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SGCG | ENST00000218867.4 | c.533delC | p.Ser178fs | frameshift_variant | Exon 6 of 8 | 1 | NM_000231.3 | ENSP00000218867.3 | ||
SACS | ENST00000683210.1 | c.2186-6199delG | intron_variant | Intron 9 of 9 | ENSP00000506739.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251462Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135900
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461794Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727204
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2C Pathogenic:1
This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SGCG-related conditions. For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Ser178*) in the SGCG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SGCG are known to be pathogenic (PMID: 18285821). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at