12-14613205-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004963.4(GUCY2C):āc.3134A>Gā(p.Gln1045Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.
Frequency
Consequence
NM_004963.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GUCY2C | NM_004963.4 | c.3134A>G | p.Gln1045Arg | missense_variant | Exon 27 of 27 | ENST00000261170.5 | NP_004954.2 | |
GUCY2C | XM_011520631.3 | c.2888A>G | p.Gln963Arg | missense_variant | Exon 27 of 27 | XP_011518933.1 | ||
PLBD1-AS1 | NR_120465.1 | n.297+279T>C | intron_variant | Intron 3 of 5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GUCY2C | ENST00000261170.5 | c.3134A>G | p.Gln1045Arg | missense_variant | Exon 27 of 27 | 1 | NM_004963.4 | ENSP00000261170.3 | ||
PLBD1-AS1 | ENST00000542401.2 | n.848+279T>C | intron_variant | Intron 2 of 4 | 4 | |||||
PLBD1-AS1 | ENST00000545424.5 | n.279+279T>C | intron_variant | Intron 3 of 4 | 3 | |||||
PLBD1-AS1 | ENST00000660979.1 | n.732-5947T>C | intron_variant | Intron 1 of 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461322Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726990
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1045 of the GUCY2C protein (p.Gln1045Arg). 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. An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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