12-14613238-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_004963.4(GUCY2C):āc.3101T>Cā(p.Leu1034Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,268 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 (ā ā ).
Frequency
Consequence
NM_004963.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GUCY2C | NM_004963.4 | c.3101T>C | p.Leu1034Ser | missense_variant | Exon 27 of 27 | ENST00000261170.5 | NP_004954.2 | |
GUCY2C | XM_011520631.3 | c.2855T>C | p.Leu952Ser | missense_variant | Exon 27 of 27 | XP_011518933.1 | ||
PLBD1-AS1 | NR_120465.1 | n.297+312A>G | intron_variant | Intron 3 of 5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GUCY2C | ENST00000261170.5 | c.3101T>C | p.Leu1034Ser | missense_variant | Exon 27 of 27 | 1 | NM_004963.4 | ENSP00000261170.3 | ||
PLBD1-AS1 | ENST00000542401.2 | n.848+312A>G | intron_variant | Intron 2 of 4 | 4 | |||||
PLBD1-AS1 | ENST00000545424.5 | n.279+312A>G | intron_variant | Intron 3 of 4 | 3 | |||||
PLBD1-AS1 | ENST00000660979.1 | n.732-5914A>G | intron_variant | Intron 1 of 3 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152060Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251036Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135666
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461208Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 726938
GnomAD4 genome AF: 0.0000395 AC: 6AN: 152060Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74266
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.3101T>C (p.L1034S) alteration is located in exon 27 (coding exon 27) of the GUCY2C gene. This alteration results from a T to C substitution at nucleotide position 3101, causing the leucine (L) at amino acid position 1034 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1034 of the GUCY2C protein (p.Leu1034Ser). This variant is present in population databases (rs746455153, gnomAD 0.003%). 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 (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