1-20633776-G-A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_032409.3(PINK1):​c.228G>A​(p.Gly76Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000046 in 1,565,598 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

PINK1
NM_032409.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.03

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: Benign. The variant received -7 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 1-20633776-G-A is Benign according to our data. Variant chr1-20633776-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3671790.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.03 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PINK1NM_032409.3 linkc.228G>A p.Gly76Gly synonymous_variant Exon 1 of 8 ENST00000321556.5 NP_115785.1 Q9BXM7-1
MIR6084NR_106732.1 linkn.98G>A non_coding_transcript_exon_variant Exon 1 of 1
MIR6084unassigned_transcript_48 n.*1G>A downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PINK1ENST00000321556.5 linkc.228G>A p.Gly76Gly synonymous_variant Exon 1 of 8 1 NM_032409.3 ENSP00000364204.3 Q9BXM7-1
MIR6084ENST00000622012.1 linkn.98G>A non_coding_transcript_exon_variant Exon 1 of 1 6

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152146
Hom.:
0
Cov.:
31
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:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000891
AC:
15
AN:
168376
AF XY:
0.000107
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000360
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000851
Gnomad NFE exome
AF:
0.0000854
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000502
AC:
71
AN:
1413452
Hom.:
0
Cov.:
35
AF XY:
0.0000471
AC XY:
33
AN XY:
700314
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32758
American (AMR)
AF:
0.00
AC:
0
AN:
38948
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25350
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37862
South Asian (SAS)
AF:
0.00
AC:
0
AN:
81456
European-Finnish (FIN)
AF:
0.000813
AC:
32
AN:
39346
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5280
European-Non Finnish (NFE)
AF:
0.0000320
AC:
35
AN:
1093636
Other (OTH)
AF:
0.0000680
AC:
4
AN:
58816
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.466
Heterozygous variant carriers
0
4
9
13
18
22
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:
0.00000657
AC:
1
AN:
152146
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74314
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41440
American (AMR)
AF:
0.00
AC:
0
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
0.0000943
AC:
1
AN:
10604
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68010
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Autosomal recessive early-onset Parkinson disease 6 Benign:1
Dec 17, 2024
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
BayesDel_noAF
Benign
-0.63
CADD
Benign
17
DANN
Benign
0.94
PhyloP100
1.0
PromoterAI
-0.027
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Mutation Taster
=100/0
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: rs781257771; hg19: chr1-20960269; API