rs571490973
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong
The NM_004562.3(PRKN):c.689C>T(p.Ala230Val) variant causes a missense change. The variant allele was found at a frequency of 0.000103 in 1,613,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. A230E) has been classified as Uncertain significance.
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.689C>T | p.Ala230Val | missense_variant | 6/12 | ENST00000366898.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKN | ENST00000366898.6 | c.689C>T | p.Ala230Val | missense_variant | 6/12 | 1 | NM_004562.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000207 AC: 52AN: 251456Hom.: 0 AF XY: 0.000287 AC XY: 39AN XY: 135896
GnomAD4 exome AF: 0.000107 AC: 156AN: 1461624Hom.: 0 Cov.: 30 AF XY: 0.000164 AC XY: 119AN XY: 727120
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152292Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74468
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 29, 2016 | This sequence change replaces alanine with valine at codon 230 of the PARK2 protein (p.Ala230Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is present in population databases (rs571490973, ExAC 0.2%) but has not been reported in the literature in individuals with a PARK2-related disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at