rs6070157
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_002591.4(PCK1):c.282C>T(p.Ile94=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,613,658 control chromosomes in the GnomAD database, including 30,555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.17 ( 2424 hom., cov: 33)
Exomes 𝑓: 0.19 ( 28131 hom. )
Consequence
PCK1
NM_002591.4 synonymous
NM_002591.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.472
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 20-57562128-C-T is Benign according to our data. Variant chr20-57562128-C-T is described in ClinVar as [Benign]. Clinvar id is 338874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
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Synonymous conserved (PhyloP=0.472 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCK1 | NM_002591.4 | c.282C>T | p.Ile94= | synonymous_variant | 3/10 | ENST00000319441.6 | |
PCK1 | XM_024451888.2 | c.10+493C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCK1 | ENST00000319441.6 | c.282C>T | p.Ile94= | synonymous_variant | 3/10 | 1 | NM_002591.4 | P1 | |
PCK1 | ENST00000467047.1 | n.1049C>T | non_coding_transcript_exon_variant | 1/2 | 1 | ||||
PCK1 | ENST00000475833.1 | n.858C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.171 AC: 26059AN: 152038Hom.: 2416 Cov.: 33
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GnomAD3 exomes AF: 0.172 AC: 43260AN: 251326Hom.: 4213 AF XY: 0.176 AC XY: 23846AN XY: 135858
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GnomAD4 exome AF: 0.191 AC: 279285AN: 1461502Hom.: 28131 Cov.: 33 AF XY: 0.192 AC XY: 139361AN XY: 727064
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GnomAD4 genome ? AF: 0.172 AC: 26099AN: 152156Hom.: 2424 Cov.: 33 AF XY: 0.170 AC XY: 12649AN XY: 74386
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | - - |
Phosphoenolpyruvate carboxykinase deficiency, cytosolic Benign:1
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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