14-24097059-C-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting
The NM_004563.4(PCK2):āc.197C>Gā(p.Thr66Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000375 in 1,613,390 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_004563.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCK2 | NM_004563.4 | c.197C>G | p.Thr66Ser | missense_variant | Exon 2 of 10 | ENST00000216780.9 | NP_004554.3 | |
NRL | NM_001354768.3 | c.-27-14184G>C | 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.197C>G | p.Thr66Ser | missense_variant | Exon 2 of 10 | 1 | NM_004563.4 | ENSP00000216780.4 | ||
NRL | ENST00000561028.6 | c.-27-14184G>C | intron_variant | Intron 1 of 2 | 2 | NM_001354768.3 | ENSP00000454062.2 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 151914Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000995 AC: 25AN: 251322Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135868
GnomAD4 exome AF: 0.000398 AC: 581AN: 1461476Hom.: 2 Cov.: 32 AF XY: 0.000378 AC XY: 275AN XY: 727072
GnomAD4 genome AF: 0.000158 AC: 24AN: 151914Hom.: 0 Cov.: 30 AF XY: 0.000135 AC XY: 10AN XY: 74170
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.197C>G (p.T66S) alteration is located in exon 2 (coding exon 2) of the PCK2 gene. This alteration results from a C to G substitution at nucleotide position 197, causing the threonine (T) at amino acid position 66 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 threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 66 of the PCK2 protein (p.Thr66Ser). This variant is present in population databases (rs200792430, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PCK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2052577). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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