1-20633595-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4BP6

The NM_032409.3(PINK1):​c.47C>T​(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000369 in 1,248,072 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

PINK1
NM_032409.3 missense

Scores

2
1
16

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.851

Publications

0 publications found
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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.30064583).
BP6
Variant 1-20633595-C-T is Benign according to our data. Variant chr1-20633595-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1374264.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PINK1NM_032409.3 linkc.47C>T p.Ala16Val missense_variant Exon 1 of 8 ENST00000321556.5 NP_115785.1 Q9BXM7-1
MIR6084NR_106732.1 linkn.-84C>T upstream_gene_variant
MIR6084unassigned_transcript_48 n.-161C>T upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PINK1ENST00000321556.5 linkc.47C>T p.Ala16Val missense_variant Exon 1 of 8 1 NM_032409.3 ENSP00000364204.3 Q9BXM7-1
MIR6084ENST00000622012.1 linkn.-84C>T upstream_gene_variant 6

Frequencies

GnomAD3 genomes
AF:
0.000139
AC:
21
AN:
151270
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000508
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:
0.00
GnomAD4 exome
AF:
0.0000228
AC:
25
AN:
1096802
Hom.:
0
Cov.:
30
AF XY:
0.0000134
AC XY:
7
AN XY:
521308
show subpopulations
African (AFR)
AF:
0.000999
AC:
22
AN:
22030
American (AMR)
AF:
0.00
AC:
0
AN:
7644
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
13766
East Asian (EAS)
AF:
0.00
AC:
0
AN:
24256
South Asian (SAS)
AF:
0.00
AC:
0
AN:
27310
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
23038
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2922
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
931848
Other (OTH)
AF:
0.0000682
AC:
3
AN:
43988
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.507
Heterozygous variant carriers
0
2
3
5
6
8
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000139
AC:
21
AN:
151270
Hom.:
0
Cov.:
32
AF XY:
0.000149
AC XY:
11
AN XY:
73890
show subpopulations
African (AFR)
AF:
0.000508
AC:
21
AN:
41322
American (AMR)
AF:
0.00
AC:
0
AN:
15192
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3462
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5176
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10210
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67764
Other (OTH)
AF:
0.00
AC:
0
AN:
2080
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.000230

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Aug 02, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.47C>T (p.A16V) alteration is located in exon 1 (coding exon 1) of the PINK1 gene. This alteration results from a C to T substitution at nucleotide position 47, causing the alanine (A) at amino acid position 16 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Autosomal recessive early-onset Parkinson disease 6 Benign:1
Mar 31, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.064
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
23
DANN
Benign
0.93
DEOGEN2
Benign
0.078
T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.40
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.70
T
M_CAP
Pathogenic
0.59
D
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-0.56
T
MutationAssessor
Benign
1.9
M
PhyloP100
0.85
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-0.45
N
REVEL
Uncertain
0.32
Sift
Benign
0.21
T
Sift4G
Benign
0.38
T
Polyphen
1.0
D
Vest4
0.16
MutPred
0.43
Loss of helix (P = 0.0033);
MVP
0.85
MPC
0.17
ClinPred
0.33
T
GERP RS
2.8
PromoterAI
0.0054
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.041
gMVP
0.21
Mutation Taster
=90/10
polymorphism

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

Other links and lift over

dbSNP: rs897203855; hg19: chr1-20960088; API