rs75860381
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM5PP3
The NM_004562.3(PRKN):c.136G>T(p.Ala46Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,782 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A46T) 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 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKN | NM_004562.3 | c.136G>T | p.Ala46Ser | missense_variant | 2/12 | ENST00000366898.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKN | ENST00000366898.6 | c.136G>T | p.Ala46Ser | missense_variant | 2/12 | 1 | NM_004562.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251364Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135848
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460782Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 726688
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 20, 2019 | 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"). This variant has been observed in an individual affected with probable dementia with Lewy bodies (PMID: 22118943). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with serine at codon 46 of the PRKN protein (p.Ala46Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at