chr20-57561418-C-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_002591.4(PCK1):c.7C>T(p.Pro3Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00173 in 1,610,994 control chromosomes in the GnomAD database, including 5 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00089 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0018 ( 5 hom. )
Consequence
PCK1
NM_002591.4 missense
NM_002591.4 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 3.65
Genes affected
PCK1 (HGNC:8724): (phosphoenolpyruvate carboxykinase 1) This gene is a main control point for the regulation of gluconeogenesis. The cytosolic enzyme encoded by this gene, along with GTP, catalyzes the formation of phosphoenolpyruvate from oxaloacetate, with the release of carbon dioxide and GDP. The expression of this gene can be regulated by insulin, glucocorticoids, glucagon, cAMP, and diet. Defects in this gene are a cause of cytosolic phosphoenolpyruvate carboxykinase deficiency. A mitochondrial isozyme of the encoded protein also has been characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.007808417).
BP6
Variant 20-57561418-C-T is Benign according to our data. Variant chr20-57561418-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 788182.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=2}. Variant chr20-57561418-C-T is described in Lovd as [Likely_benign].
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCK1 | NM_002591.4 | c.7C>T | p.Pro3Ser | missense_variant | 2/10 | ENST00000319441.6 | |
PCK1 | XM_024451888.2 | c.-208C>T | 5_prime_UTR_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCK1 | ENST00000319441.6 | c.7C>T | p.Pro3Ser | missense_variant | 2/10 | 1 | NM_002591.4 | P1 | |
PCK1 | ENST00000467047.1 | n.339C>T | non_coding_transcript_exon_variant | 1/2 | 1 | ||||
PCK1 | ENST00000475833.1 | n.148C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000887 AC: 135AN: 152196Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00132 AC: 330AN: 249344Hom.: 0 AF XY: 0.00134 AC XY: 181AN XY: 134794
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GnomAD4 exome AF: 0.00182 AC: 2657AN: 1458680Hom.: 5 Cov.: 29 AF XY: 0.00179 AC XY: 1300AN XY: 725466
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GnomAD4 genome AF: 0.000886 AC: 135AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.000752 AC XY: 56AN XY: 74472
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Phosphoenolpyruvate carboxykinase deficiency, cytosolic Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 19, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
PCK1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 09, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at