rs754573542
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_015488.5(PNKD):c.854C>A(p.Thr285Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,612,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T285T) has been classified as Likely benign.
Frequency
Consequence
NM_015488.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNKD | NM_015488.5 | c.854C>A | p.Thr285Asn | missense_variant | 8/10 | ENST00000273077.9 | |
CATIP-AS2 | NR_125777.1 | n.120+7588G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNKD | ENST00000273077.9 | c.854C>A | p.Thr285Asn | missense_variant | 8/10 | 1 | NM_015488.5 | ||
CATIP-AS2 | ENST00000411433.1 | n.120+7588G>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152152Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460456Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726384
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152152Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74324
ClinVar
Submissions by phenotype
Paroxysmal nonkinesigenic dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 11, 2022 | 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. 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"). ClinVar contains an entry for this variant (Variation ID: 574145). This variant has not been reported in the literature in individuals affected with PNKD-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 285 of the PNKD protein (p.Thr285Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at