rs9456711

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004562.3(PRKN):ā€‹c.783A>Gā€‹(p.Leu261Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00951 in 1,614,066 control chromosomes in the GnomAD database, including 1,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.051 ( 662 hom., cov: 33)
Exomes š‘“: 0.0052 ( 624 hom. )

Consequence

PRKN
NM_004562.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.995
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 6-161785860-T-C is Benign according to our data. Variant chr6-161785860-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 356017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-161785860-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.995 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PRKNNM_004562.3 linkuse as main transcriptc.783A>G p.Leu261Leu synonymous_variant 7/12 ENST00000366898.6 NP_004553.2 O60260-1X5DR79

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PRKNENST00000366898.6 linkuse as main transcriptc.783A>G p.Leu261Leu synonymous_variant 7/121 NM_004562.3 ENSP00000355865.1 O60260-1

Frequencies

GnomAD3 genomes
AF:
0.0504
AC:
7675
AN:
152132
Hom.:
657
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.176
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0170
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000827
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000647
Gnomad OTH
AF:
0.0368
GnomAD3 exomes
AF:
0.0133
AC:
3340
AN:
251288
Hom.:
297
AF XY:
0.00944
AC XY:
1282
AN XY:
135818
show subpopulations
Gnomad AFR exome
AF:
0.182
Gnomad AMR exome
AF:
0.00758
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000392
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000625
Gnomad OTH exome
AF:
0.00701
GnomAD4 exome
AF:
0.00522
AC:
7636
AN:
1461816
Hom.:
624
Cov.:
32
AF XY:
0.00447
AC XY:
3254
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.180
Gnomad4 AMR exome
AF:
0.00917
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000452
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000347
Gnomad4 OTH exome
AF:
0.0121
GnomAD4 genome
AF:
0.0506
AC:
7707
AN:
152250
Hom.:
662
Cov.:
33
AF XY:
0.0483
AC XY:
3595
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.176
Gnomad4 AMR
AF:
0.0169
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000647
Gnomad4 OTH
AF:
0.0364
Alfa
AF:
0.0110
Hom.:
193
Bravo
AF:
0.0568
Asia WGS
AF:
0.0130
AC:
46
AN:
3478
EpiCase
AF:
0.000709
EpiControl
AF:
0.000474

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:4
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsDec 07, 2017- -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 22, 2024- -
Benign, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsDec 30, 2016- -
Autosomal recessive juvenile Parkinson disease 2 Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
CADD
Benign
3.8
DANN
Benign
0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9456711; hg19: chr6-162206892; API