NM_032409.3:c.1196C>T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_032409.3(PINK1):c.1196C>T(p.Pro399Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000867 in 1,614,172 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 (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
PINK1
NM_032409.3 missense
NM_032409.3 missense
Scores
8
7
4
Clinical Significance
Conservation
PhyloP100: 7.06
Genes affected
PINK1 (HGNC:14581): (PTEN induced kinase 1) This gene encodes a serine/threonine protein kinase that localizes to mitochondria. It is thought to protect cells from stress-induced mitochondrial dysfunction. Mutations in this gene cause one form of autosomal recessive early-onset Parkinson disease. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.909
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PINK1 | ENST00000321556.5 | c.1196C>T | p.Pro399Leu | missense_variant | Exon 6 of 8 | 1 | NM_032409.3 | ENSP00000364204.3 | ||
PINK1 | ENST00000400490.2 | n.289C>T | non_coding_transcript_exon_variant | Exon 2 of 4 | 2 | |||||
PINK1-AS | ENST00000451424.1 | n.3617G>A | non_coding_transcript_exon_variant | Exon 1 of 3 | 2 | |||||
PINK1 | ENST00000492302.1 | n.2284C>T | non_coding_transcript_exon_variant | Exon 4 of 5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251240Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135854
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GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461856Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727228
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152316Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74498
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Parkinson disease, autosomal recessive early-onset, digenic, PINK1/DJ1 Pathogenic:1
Jun 01, 2006
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Benign
M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at P399 (P = 0.0093);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at