6-161629292-C-T

Variant names:

• chr6-161629292-C-T
• rs2144208
• NM_004562.3:c.872-59876G>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.872-59876G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,978 control chromosomes in the GnomAD database, including 3,568 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 0.21 (3568 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKN	NM_004562.3	MANE Select	c.872-59876G>A		intron	N/A	NP_004553.2
	PRKN	NM_013987.3		c.788-59876G>A		intron	N/A	NP_054642.2
	PRKN	NM_013988.3		c.425-59876G>A		intron	N/A	NP_054643.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKN	ENST00000366898.6	TSL:1 MANE Select	c.872-59876G>A		intron	N/A	ENSP00000355865.1
	PRKN	ENST00000366897.5	TSL:1	c.788-59876G>A		intron	N/A	ENSP00000355863.1
	PRKN	ENST00000366896.5	TSL:1	c.425-59876G>A		intron	N/A	ENSP00000355862.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32362 AN: 151860 Hom.: 3568 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.213 AC: 32370 AN: 151978 Hom.: 3568 Cov.: 32 AF XY: 0.211 AC XY: 15706 AN XY: 74306

African (AFR) AF: 0.230 AC: 9541 AN: 41446

American (AMR) AF: 0.130 AC: 1984 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3466

East Asian (EAS) AF: 0.185 AC: 951 AN: 5150

South Asian (SAS) AF: 0.144 AC: 692 AN: 4822

European-Finnish (FIN) AF: 0.259 AC: 2732 AN: 10566

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15448 AN: 67928

Other (OTH) AF: 0.200 AC: 423 AN: 2112

Alfa AF: 0.212 Hom.: 10745

Bravo AF: 0.204

Asia WGS AF: 0.193 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.31
DANN	Benign	0.71
PhyloP100		-1.0
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: rs2144208; hg19: chr6-162050324; COSMIC: COSV58209632;