14-24097041-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_004563.4(PCK2):āc.179T>Cā(p.Ile60Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,320 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 ).
Frequency
Consequence
NM_004563.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCK2 | NM_004563.4 | c.179T>C | p.Ile60Thr | missense_variant | Exon 2 of 10 | ENST00000216780.9 | NP_004554.3 | |
NRL | NM_001354768.3 | c.-27-14166A>G | intron_variant | Intron 1 of 2 | ENST00000561028.6 | NP_001341697.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCK2 | ENST00000216780.9 | c.179T>C | p.Ile60Thr | missense_variant | Exon 2 of 10 | 1 | NM_004563.4 | ENSP00000216780.4 | ||
NRL | ENST00000561028.6 | c.-27-14166A>G | intron_variant | Intron 1 of 2 | 2 | NM_001354768.3 | ENSP00000454062.2 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151680Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251348Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135872
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461640Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727144
GnomAD4 genome AF: 0.00000659 AC: 1AN: 151680Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74056
ClinVar
Submissions by phenotype
not provided Uncertain:1
This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 60 of the PCK2 protein (p.Ile60Thr). This variant has not been reported in the literature in individuals affected with PCK2-related conditions. 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PCK2 protein function. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at