15-100924682-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_024652.6(LRRK1):c.50C>T(p.Pro17Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,614,026 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 (★). Synonymous variant affecting the same amino acid position (i.e. P17P) has been classified as Likely benign.
Frequency
Consequence
NM_024652.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRK1 | NM_024652.6 | c.50C>T | p.Pro17Leu | missense_variant | 2/34 | ENST00000388948.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRK1 | ENST00000388948.8 | c.50C>T | p.Pro17Leu | missense_variant | 2/34 | 5 | NM_024652.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000724 AC: 11AN: 152038Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000836 AC: 21AN: 251236Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135828
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461870Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16AN XY: 727230
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74392
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 03, 2022 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with LRRK1-related conditions. This variant is present in population databases (rs180759486, gnomAD 0.1%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 17 of the LRRK1 protein (p.Pro17Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at