chr13-23295438-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000231.3(SGCG):c.529C>T(p.His177Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000231.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SGCG | ENST00000218867.4 | c.529C>T | p.His177Tyr | missense_variant | Exon 6 of 8 | 1 | NM_000231.3 | ENSP00000218867.3 | ||
SACS | ENST00000683210.1 | c.2186-6195G>A | intron_variant | Intron 9 of 9 | ENSP00000506739.1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152130Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251462Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135898
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461758Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727188
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74448
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2C Uncertain:2
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This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 177 of the SGCG protein (p.His177Tyr). This variant is present in population databases (rs375592456, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with SGCG-related conditions. ClinVar contains an entry for this variant (Variation ID: 966298). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SGCG protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at