chr20-57561562-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002591.4(PCK1):c.151G>A(p.Glu51Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002591.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCK1 | NM_002591.4 | c.151G>A | p.Glu51Lys | missense_variant | 2/10 | ENST00000319441.6 | |
PCK1 | XM_024451888.2 | c.-64G>A | 5_prime_UTR_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCK1 | ENST00000319441.6 | c.151G>A | p.Glu51Lys | missense_variant | 2/10 | 1 | NM_002591.4 | P1 | |
PCK1 | ENST00000467047.1 | n.483G>A | non_coding_transcript_exon_variant | 1/2 | 1 | ||||
PCK1 | ENST00000475833.1 | n.292G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461708Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727132
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 25, 2023 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt PCK1 protein function. This variant has not been reported in the literature in individuals affected with PCK1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 51 of the PCK1 protein (p.Glu51Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at