1-20633636-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_032409.3(PINK1):c.88G>A(p.Gly30Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,318,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G30R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PINK1
NM_032409.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.390

Publications

5 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]

PINK1 links:

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]

MIR6084 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11801562).

BP6

Variant 1-20633636-G-A is Benign according to our data. Variant chr1-20633636-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2767231.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PINK1	NM_032409.3 link	c.88G>A	p.Gly30Ser	missense_variant	Exon 1 of 8	ENST00000321556.5	NP_115785.1	Q9BXM7-1
MIR6084	NR_106732.1 link	n.-43G>A		upstream_gene_variant
MIR6084	unassigned_transcript_48	n.-120G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PINK1	ENST00000321556.5 link	c.88G>A	p.Gly30Ser	missense_variant	Exon 1 of 8	1	NM_032409.3	ENSP00000364204.3		Q9BXM7-1
MIR6084	ENST00000622012.1 link	n.-43G>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.000119

AC:

AN:

151082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000412

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:

0.000483

GnomAD2 exomes

AF:

0.00

AC:

AN:

1076

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1167630

Hom.:

Cov.:

AF XY:

0.0000106

AC XY:

AN XY:

563504

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

22868

American (AMR)

AF:

0.00

AC:

AN:

8450

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15364

East Asian (EAS)

AF:

0.00

AC:

AN:

26100

South Asian (SAS)

AF:

0.00

AC:

AN:

41740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27016

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3222

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

975324

Other (OTH)

AF:

0.0000421

AC:

AN:

47546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000119

AC:

AN:

151188

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

73876

show subpopulations

African (AFR)

AF:

0.000410

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67544

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000128

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

Jul 31, 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.071

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.71

PhyloP100

0.39

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.49

REVEL

Benign

0.033

Sift

Benign

0.035

Sift4G

Benign

0.16

Polyphen

0.015

Vest4

0.11

MVP

0.72

MPC

0.17

ClinPred

0.095

GERP RS

2.5

PromoterAI

-0.034

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.079

gMVP

0.46

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-20633636-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over