rs768233445
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4BP6BS1BS2
The NM_003919.3(SGCE):c.470C>T(p.Pro157Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000273 in 1,611,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_003919.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SGCE | NM_003919.3 | c.470C>T | p.Pro157Leu | missense_variant | Exon 5 of 11 | ENST00000648936.2 | NP_003910.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152046Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000761 AC: 19AN: 249616Hom.: 0 AF XY: 0.0000667 AC XY: 9AN XY: 135024
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1459490Hom.: 0 Cov.: 29 AF XY: 0.0000234 AC XY: 17AN XY: 726244
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152046Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74268
ClinVar
Submissions by phenotype
Myoclonic dystonia 11 Uncertain:2Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 157 of the SGCE protein (p.Pro157Leu). This variant is present in population databases (rs768233445, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SGCE-related conditions. ClinVar contains an entry for this variant (Variation ID: 464156). 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 not expected to disrupt SGCE protein function with a negative 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. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at