rs587784572
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_004963.4(GUCY2C):c.2008G>A(p.Ala670Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign 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 Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GUCY2C | NM_004963.4 | c.2008G>A | p.Ala670Thr | missense_variant | 18/27 | ENST00000261170.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GUCY2C | ENST00000261170.5 | c.2008G>A | p.Ala670Thr | missense_variant | 18/27 | 1 | NM_004963.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 152090Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251246Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135772
GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461346Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20AN XY: 726988
GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 152090Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74298
ClinVar
Submissions by phenotype
Meconium ileus Pathogenic:1
Pathogenic, no assertion criteria provided | research | FORGE Canada, Children's Hospital of Eastern Ontario | Aug 13, 2014 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 670 of the GUCY2C protein (p.Ala670Thr). This variant is present in population databases (rs587784572, gnomAD 0.01%). This missense change has been observed in individual(s) with autosomal recessive meconium ileus (PMID: 25370039). ClinVar contains an entry for this variant (Variation ID: 161158). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GUCY2C protein function with a negative predictive value of 80%. 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