12-14669773-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004963.4(GUCY2C):c.1231C>G(p.Pro411Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004963.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GUCY2C | NM_004963.4 | c.1231C>G | p.Pro411Ala | missense_variant | Exon 10 of 27 | ENST00000261170.5 | NP_004954.2 | |
GUCY2C | XM_011520631.3 | c.985C>G | p.Pro329Ala | missense_variant | Exon 10 of 27 | XP_011518933.1 | ||
GUCY2C-AS1 | NR_186173.1 | n.335+1627G>C | intron_variant | Intron 3 of 5 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 26
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74298
ClinVar
Submissions by phenotype
not provided Uncertain:1
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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GUCY2C protein function. This variant has not been reported in the literature in individuals affected with GUCY2C-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 411 of the GUCY2C protein (p.Pro411Ala). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at