22-20709921-TTGTC-T
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_058004.4(PI4KA):c.6156_6159delGACA(p.Thr2053SerfsTer4) variant causes a frameshift change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_058004.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00 AC: 19AN: 151192Hom.: 0 Cov.: 29 FAILED QC
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000281 AC: 41AN: 1457260Hom.: 0 AF XY: 0.0000303 AC XY: 22AN XY: 725300
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000132 AC: 20AN: 151288Hom.: 0 Cov.: 29 AF XY: 0.000203 AC XY: 15AN XY: 73846
ClinVar
Submissions by phenotype
Spastic paraplegia 84, autosomal recessive Pathogenic:2
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Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis Pathogenic:1
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not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Thr2053Serfs*4) in the PI4KA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PI4KA are known to be pathogenic (PMID: 34415322). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with PI4KA-related condition (PMID: 34415322). ClinVar contains an entry for this variant (Variation ID: 1325874). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at