Genetic Variant PRKN:c.7+6092A>G (chr6-162721570-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004562.3(PRKN):c.7+6092A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,164 control chromosomes in the GnomAD database, including 3,096 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 3096 hom., cov: 32)

Consequence

PRKN
NM_004562.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0800

Publications

4 publications found

Variant links:

Genes affected

PRKN (HGNC:8607): (parkin RBR E3 ubiquitin protein ligase) The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice variants of this gene have been described but currently lack transcript support. [provided by RefSeq, Jul 2008]

PRKN Gene-Disease associations (from GenCC):

autosomal recessive juvenile Parkinson disease 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp
Parkinson disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
young-onset Parkinson disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PRKN links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004562.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRKN	NM_004562.3	MANE Select	c.7+6092A>G	intron	N/A	NP_004553.2	O60260-1
PRKN	NM_013987.3		c.7+6092A>G	intron	N/A	NP_054642.2	O60260-2
PRKN	NM_013988.3		c.7+6092A>G	intron	N/A	NP_054643.2	O60260-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRKN	ENST00000366898.6	TSL:1 MANE Select	c.7+6092A>G	intron	N/A	ENSP00000355865.1	O60260-1
PRKN	ENST00000366897.5	TSL:1	c.7+6092A>G	intron	N/A	ENSP00000355863.1	O60260-2
PRKN	ENST00000366896.5	TSL:1	c.7+6092A>G	intron	N/A	ENSP00000355862.1	O60260-6

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27029

AN:

152046

Hom.:

3095

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0518

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.174

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.178

AC:

27023

AN:

152164

Hom.:

3096

Cov.:

AF XY:

0.186

AC XY:

13809

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0517

AC:

2147

AN:

41564

American (AMR)

AF:

0.161

AC:

2455

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

443

AN:

3466

East Asian (EAS)

AF:

0.476

AC:

2450

AN:

5150

South Asian (SAS)

AF:

0.297

AC:

1430

AN:

4810

European-Finnish (FIN)

AF:

0.288

AC:

3052

AN:

10580

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14296

AN:

67982

Other (OTH)

AF:

0.174

AC:

368

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1052

2105

3157

4210

5262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.166

Hom.:

390

Bravo

AF:

0.164

Asia WGS

AF:

0.317

AC:

1103

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.2

(source)

DANN

Benign

0.76

PhyloP100

0.080

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over