12-14613272-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_004963.4(GUCY2C):c.3067C>T(p.Gln1023*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004963.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GUCY2C | NM_004963.4 | c.3067C>T | p.Gln1023* | stop_gained | Exon 27 of 27 | ENST00000261170.5 | NP_004954.2 | |
GUCY2C | XM_011520631.3 | c.2821C>T | p.Gln941* | stop_gained | Exon 27 of 27 | XP_011518933.1 | ||
PLBD1-AS1 | NR_120465.1 | n.297+346G>A | intron_variant | Intron 3 of 5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GUCY2C | ENST00000261170.5 | c.3067C>T | p.Gln1023* | stop_gained | Exon 27 of 27 | 1 | NM_004963.4 | ENSP00000261170.3 | ||
PLBD1-AS1 | ENST00000542401.2 | n.848+346G>A | intron_variant | Intron 2 of 4 | 4 | |||||
PLBD1-AS1 | ENST00000545424.5 | n.279+346G>A | intron_variant | Intron 3 of 4 | 3 | |||||
PLBD1-AS1 | ENST00000660979.1 | n.732-5880G>A | intron_variant | Intron 1 of 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change creates a premature translational stop signal (p.Gln1023*) in the GUCY2C gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 51 amino acid(s) of the GUCY2C protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GUCY2C-related conditions. ClinVar contains an entry for this variant (Variation ID: 1020157). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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