dbSNP rs2053014865: PINK1:p.Phe21Leu (chr1-20633611-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032409.3(PINK1):c.63C>A(p.Phe21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F21F) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PINK1
NM_032409.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.21

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]

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17220733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PINK1	NM_032409.3 link	c.63C>A	p.Phe21Leu	missense_variant	Exon 1 of 8	ENST00000321556.5	NP_115785.1	Q9BXM7-1
MIR6084	NR_106732.1 link	n.-68C>A		upstream_gene_variant
MIR6084	unassigned_transcript_48	n.-145C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PINK1	ENST00000321556.5 link	c.63C>A	p.Phe21Leu	missense_variant	Exon 1 of 8	1	NM_032409.3	ENSP00000364204.3		Q9BXM7-1
MIR6084	ENST00000622012.1 link	n.-68C>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1131708

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

541786

African (AFR)

AF:

0.00

AC:

AN:

22414

American (AMR)

AF:

0.00

AC:

AN:

7960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14576

East Asian (EAS)

AF:

0.00

AC:

AN:

25074

South Asian (SAS)

AF:

0.00

AC:

AN:

34114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25032

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3064

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

953636

Other (OTH)

AF:

0.00

AC:

AN:

45838

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.46

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.3

PhyloP100

1.2

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-1.6

REVEL

Benign

0.17

Sift

Benign

0.28

Sift4G

Benign

0.52

Polyphen

0.0020

Vest4

0.17

MutPred

0.37

Gain of disorder (P = 0.0357);

MVP

0.87

MPC

0.20

ClinPred

0.35

GERP RS

3.6

PromoterAI

0.0058

Neutral

(source)

Varity_R

0.22

gMVP

0.28

Mutation Taster

=90/10

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over