chr19-49861253-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_007254.4(PNKP):c.1561G>A(p.Gly521Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000816 in 1,593,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_007254.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250348Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135628
GnomAD4 exome AF: 0.00000763 AC: 11AN: 1441696Hom.: 0 Cov.: 29 AF XY: 0.00000696 AC XY: 5AN XY: 718644
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74334
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 12 Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 521 of the PNKP protein (p.Gly521Ser). This variant has not been reported in the literature in individuals affected with PNKP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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