2-218344559-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000273077.9(PNKD):c.973C>T(p.Arg325Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000271 in 1,587,104 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R325H) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000273077.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PNKD | NM_015488.5 | c.973C>T | p.Arg325Cys | missense_variant | 9/10 | ENST00000273077.9 | NP_056303.3 | |
CATIP-AS2 | NR_125777.1 | n.120+6601G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PNKD | ENST00000273077.9 | c.973C>T | p.Arg325Cys | missense_variant | 9/10 | 1 | NM_015488.5 | ENSP00000273077 | ||
CATIP-AS2 | ENST00000411433.1 | n.120+6601G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152150Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000446 AC: 9AN: 201948Hom.: 0 AF XY: 0.0000643 AC XY: 7AN XY: 108854
GnomAD4 exome AF: 0.0000244 AC: 35AN: 1434836Hom.: 0 Cov.: 31 AF XY: 0.0000253 AC XY: 18AN XY: 711722
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152268Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74456
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 06, 2021 | The c.973C>T (p.R325C) alteration is located in exon 9 (coding exon 9) of the PNKD gene. This alteration results from a C to T substitution at nucleotide position 973, causing the arginine (R) at amino acid position 325 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Paroxysmal nonkinesigenic dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 18, 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 PNKD protein function. ClinVar contains an entry for this variant (Variation ID: 241062). This variant has not been reported in the literature in individuals affected with PNKD-related conditions. This variant is present in population databases (rs149750691, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 325 of the PNKD protein (p.Arg325Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at