12-14613262-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004963.4(GUCY2C):āc.3077T>Gā(p.Phe1026Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,294 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_004963.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GUCY2C | NM_004963.4 | c.3077T>G | p.Phe1026Cys | missense_variant | Exon 27 of 27 | ENST00000261170.5 | NP_004954.2 | |
GUCY2C | XM_011520631.3 | c.2831T>G | p.Phe944Cys | missense_variant | Exon 27 of 27 | XP_011518933.1 | ||
PLBD1-AS1 | NR_120465.1 | n.297+336A>C | intron_variant | Intron 3 of 5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GUCY2C | ENST00000261170.5 | c.3077T>G | p.Phe1026Cys | missense_variant | Exon 27 of 27 | 1 | NM_004963.4 | ENSP00000261170.3 | ||
PLBD1-AS1 | ENST00000542401.2 | n.848+336A>C | intron_variant | Intron 2 of 4 | 4 | |||||
PLBD1-AS1 | ENST00000545424.5 | n.279+336A>C | intron_variant | Intron 3 of 4 | 3 | |||||
PLBD1-AS1 | ENST00000660979.1 | n.732-5890A>C | intron_variant | Intron 1 of 3 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461224Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726928
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74278
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.3077T>G (p.F1026C) alteration is located in exon 27 (coding exon 27) of the GUCY2C gene. This alteration results from a T to G substitution at nucleotide position 3077, causing the phenylalanine (F) at amino acid position 1026 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 1026 of the GUCY2C protein (p.Phe1026Cys). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at