1-20633709-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032409.3(PINK1):​c.161C>A​(p.Ala54Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 1,519,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

PINK1
NM_032409.3 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00800
Variant links:
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]
MIR6084 (HGNC:50235): (microRNA 6084) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17004126).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PINK1NM_032409.3 linkuse as main transcriptc.161C>A p.Ala54Glu missense_variant 1/8 ENST00000321556.5
MIR6084NR_106732.1 linkuse as main transcriptn.31C>A non_coding_transcript_exon_variant 1/1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PINK1ENST00000321556.5 linkuse as main transcriptc.161C>A p.Ala54Glu missense_variant 1/81 NM_032409.3 P1Q9BXM7-1
MIR6084ENST00000622012.1 linkuse as main transcriptn.31C>A non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151818
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000480
GnomAD4 exome
AF:
0.00000658
AC:
9
AN:
1367200
Hom.:
0
Cov.:
31
AF XY:
0.00000890
AC XY:
6
AN XY:
674112
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000653
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151818
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74144
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000480
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Autosomal recessive early-onset Parkinson disease 6 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingBaylor GeneticsNov 04, 2019This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.099
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.083
T
Eigen
Benign
-0.68
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.46
T
M_CAP
Pathogenic
0.37
D
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.80
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
1.0
N
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-0.63
N
REVEL
Benign
0.10
Sift
Uncertain
0.014
D
Sift4G
Benign
0.31
T
Polyphen
0.50
P
Vest4
0.19
MutPred
0.16
Gain of solvent accessibility (P = 0.0097);
MVP
0.82
MPC
0.31
ClinPred
0.15
T
GERP RS
1.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.14
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs867771554; hg19: chr1-20960202; COSMIC: COSV58632288; COSMIC: COSV58632288; API