12-14613194-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BS1_Supporting
The NM_004963.4(GUCY2C):c.3145C>T(p.Arg1049Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,613,090 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
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GUCY2C | NM_004963.4 | c.3145C>T | p.Arg1049Trp | missense_variant | Exon 27 of 27 | ENST00000261170.5 | NP_004954.2 | |
GUCY2C | XM_011520631.3 | c.2899C>T | p.Arg967Trp | missense_variant | Exon 27 of 27 | XP_011518933.1 | ||
PLBD1-AS1 | NR_120465.1 | n.297+268G>A | intron_variant | Intron 3 of 5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GUCY2C | ENST00000261170.5 | c.3145C>T | p.Arg1049Trp | missense_variant | Exon 27 of 27 | 1 | NM_004963.4 | ENSP00000261170.3 | ||
PLBD1-AS1 | ENST00000542401.2 | n.848+268G>A | intron_variant | Intron 2 of 4 | 4 | |||||
PLBD1-AS1 | ENST00000545424.5 | n.279+268G>A | intron_variant | Intron 3 of 4 | 3 | |||||
PLBD1-AS1 | ENST00000660979.1 | n.732-5958G>A | intron_variant | Intron 1 of 3 |
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 152072Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000717 AC: 18AN: 251212Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135778
GnomAD4 exome AF: 0.000130 AC: 190AN: 1461018Hom.: 0 Cov.: 30 AF XY: 0.000120 AC XY: 87AN XY: 726838
GnomAD4 genome AF: 0.0000658 AC: 10AN: 152072Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74282
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1049 of the GUCY2C protein (p.Arg1049Trp). This variant is present in population databases (rs140551603, gnomAD 0.01%). 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: 1520722). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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