chr20-57561475-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_002591.4(PCK1):āc.64A>Gā(p.Ser22Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00049 in 1,613,876 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_002591.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCK1 | NM_002591.4 | c.64A>G | p.Ser22Gly | missense_variant | 2/10 | ENST00000319441.6 | |
PCK1 | XM_024451888.2 | c.-151A>G | 5_prime_UTR_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCK1 | ENST00000319441.6 | c.64A>G | p.Ser22Gly | missense_variant | 2/10 | 1 | NM_002591.4 | P1 | |
PCK1 | ENST00000467047.1 | n.396A>G | non_coding_transcript_exon_variant | 1/2 | 1 | ||||
PCK1 | ENST00000475833.1 | n.205A>G | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000434 AC: 66AN: 152226Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000247 AC: 62AN: 251178Hom.: 0 AF XY: 0.000236 AC XY: 32AN XY: 135756
GnomAD4 exome AF: 0.000496 AC: 725AN: 1461532Hom.: 0 Cov.: 30 AF XY: 0.000486 AC XY: 353AN XY: 727050
GnomAD4 genome AF: 0.000433 AC: 66AN: 152344Hom.: 1 Cov.: 33 AF XY: 0.000349 AC XY: 26AN XY: 74486
ClinVar
Submissions by phenotype
Phosphoenolpyruvate carboxykinase deficiency, cytosolic Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 06, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 04, 2023 | The c.64A>G (p.S22G) alteration is located in exon 2 (coding exon 1) of the PCK1 gene. This alteration results from a A to G substitution at nucleotide position 64, causing the serine (S) at amino acid position 22 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2022 | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 22 of the PCK1 protein (p.Ser22Gly). This variant is present in population databases (rs140235265, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with PCK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 896030). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine 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