rs185906233
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000273077.9(PNKD):āc.1102C>Gā(p.Arg368Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R368W) has been classified as Likely benign.
Frequency
Consequence
ENST00000273077.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PNKD | NM_015488.5 | c.1102C>G | p.Arg368Gly | missense_variant | 10/10 | ENST00000273077.9 | NP_056303.3 | |
CATIP-AS2 | NR_125777.1 | n.120+6235G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PNKD | ENST00000273077.9 | c.1102C>G | p.Arg368Gly | missense_variant | 10/10 | 1 | NM_015488.5 | ENSP00000273077 | ||
CATIP-AS2 | ENST00000411433.1 | n.120+6235G>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249452Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135292
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461708Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 727162
GnomAD4 genome AF: 0.000118 AC: 18AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74344
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 09, 2023 | The c.1102C>G (p.R368G) alteration is located in exon 10 (coding exon 10) of the PNKD gene. This alteration results from a C to G substitution at nucleotide position 1102, causing the arginine (R) at amino acid position 368 to be replaced by a glycine (G). 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 | Jan 21, 2024 | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 368 of the PNKD protein (p.Arg368Gly). This variant is present in population databases (rs185906233, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with PNKD-related conditions. ClinVar contains an entry for this variant (Variation ID: 468623). 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 with a negative predictive value of 80%. 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