rs6924502

Variant names:

• chr6-162089997-C-T
• rs6924502
• NM_004562.3:c.535-35823G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004562.3(PRKN):​c.535-35823G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,110 control chromosomes in the GnomAD database, including 43,945 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 0.76 (43945 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 6 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKN	NM_004562.3	MANE Select	c.535-35823G>A		intron	N/A	NP_004553.2
	PRKN	NM_013987.3		c.534+111134G>A		intron	N/A	NP_054642.2
	PRKN	NM_013988.3		c.172-116580G>A		intron	N/A	NP_054643.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKN	ENST00000366898.6	TSL:1 MANE Select	c.535-35823G>A		intron	N/A	ENSP00000355865.1
	PRKN	ENST00000366897.5	TSL:1	c.534+111134G>A		intron	N/A	ENSP00000355863.1
	PRKN	ENST00000366896.5	TSL:1	c.172-116580G>A		intron	N/A	ENSP00000355862.1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114978 AN: 151992 Hom.: 43899 Cov.: 32

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.745

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

GnomAD4 genome AF: 0.757 AC: 115078 AN: 152110 Hom.: 43945 Cov.: 32 AF XY: 0.758 AC XY: 56343 AN XY: 74336

African (AFR) AF: 0.865 AC: 35904 AN: 41496

American (AMR) AF: 0.731 AC: 11169 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2600 AN: 3470

East Asian (EAS) AF: 0.860 AC: 4448 AN: 5172

South Asian (SAS) AF: 0.714 AC: 3444 AN: 4826

European-Finnish (FIN) AF: 0.726 AC: 7660 AN: 10558

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47306 AN: 68002

Other (OTH) AF: 0.746 AC: 1575 AN: 2110

Alfa AF: 0.720 Hom.: 10012

Bravo AF: 0.765

Asia WGS AF: 0.813 AC: 2825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.73
DANN	Benign	0.63
PhyloP100		-0.26
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

Other links and lift over

dbSNP: rs6924502; hg19: chr6-162511029;