rs746215864
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004562.3(PRKN):c.1001G>A(p.Arg334His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. R334C) has been classified as Likely benign.
Frequency
Consequence
NM_004562.3 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 | UniProt |
---|---|---|---|---|---|---|---|
PRKN | NM_004562.3 | c.1001G>A | p.Arg334His | missense_variant | 9/12 | ENST00000366898.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKN | ENST00000366898.6 | c.1001G>A | p.Arg334His | missense_variant | 9/12 | 1 | NM_004562.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251028Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135800
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461672Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727154
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152146Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74308
ClinVar
Submissions by phenotype
Lung cancer;C0919267:Ovarian neoplasm;C1868675:Autosomal recessive juvenile Parkinson disease 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 05, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 16, 2017 | In summary, this variant has uncertain impact on PARK2 function. The available evidence is currently insufficient to determine its role 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been reported in the heterozygous state in an individual affected with Parkinson's disease (PMID: 18927607). This variant is present in population databases (rs746215864, ExAC 0.02%). This sequence change replaces arginine with histidine at codon 334 of the PARK2 protein (p.Arg334His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at