6-161815043-C-T

Variant summary

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

The NM_004562.3(PRKN):​c.735-29135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,158 control chromosomes in the GnomAD database, including 61,459 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 0.90 ( 61459 hom., cov: 31)

Consequence

PRKN
NM_004562.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0110

Publications

15 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

Genome browser will be placed here

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=-0.97).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRKNNM_004562.3 linkc.735-29135G>A intron_variant Intron 6 of 11 ENST00000366898.6 NP_004553.2 O60260-1X5DR79

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRKNENST00000366898.6 linkc.735-29135G>A intron_variant Intron 6 of 11 1 NM_004562.3 ENSP00000355865.1 O60260-1

Frequencies

GnomAD3 genomes
AF:
0.898
AC:
136558
AN:
152040
Hom.:
61427
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.922
Gnomad AMI
AF:
0.833
Gnomad AMR
AF:
0.923
Gnomad ASJ
AF:
0.870
Gnomad EAS
AF:
0.893
Gnomad SAS
AF:
0.780
Gnomad FIN
AF:
0.865
Gnomad MID
AF:
0.825
Gnomad NFE
AF:
0.895
Gnomad OTH
AF:
0.885
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.898
AC:
136642
AN:
152158
Hom.:
61459
Cov.:
31
AF XY:
0.894
AC XY:
66506
AN XY:
74376
show subpopulations
African (AFR)
AF:
0.922
AC:
38297
AN:
41532
American (AMR)
AF:
0.923
AC:
14109
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.870
AC:
3019
AN:
3470
East Asian (EAS)
AF:
0.893
AC:
4604
AN:
5158
South Asian (SAS)
AF:
0.779
AC:
3747
AN:
4808
European-Finnish (FIN)
AF:
0.865
AC:
9147
AN:
10580
Middle Eastern (MID)
AF:
0.812
AC:
237
AN:
292
European-Non Finnish (NFE)
AF:
0.895
AC:
60865
AN:
68014
Other (OTH)
AF:
0.879
AC:
1857
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
726
1452
2179
2905
3631
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
904
1808
2712
3616
4520
<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:
0.894
Hom.:
278526
Bravo
AF:
0.906
Asia WGS
AF:
0.814
AC:
2834
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
1.7
DANN
Benign
0.70
PhyloP100
-0.011
Mutation Taster
=100/0
polymorphism (auto)

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: rs3016539; hg19: chr6-162236075; API