6-162086658-A-G

Variant names:

• chr6-162086658-A-G
• rs1893551
• NM_004562.3:c.535-32484T>C

Variant summary

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

The NM_004562.3(PRKN):​c.535-32484T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,140 control chromosomes in the GnomAD database, including 45,220 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 0.77 (45220 hom., cov: 33)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 7 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 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.535-32484T>C		intron	N/A	NP_004553.2
	PRKN	NM_013987.3		c.535-113241T>C		intron	N/A	NP_054642.2
	PRKN	NM_013988.3		c.172-113241T>C		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.535-32484T>C		intron	N/A	ENSP00000355865.1
	PRKN	ENST00000366897.5	TSL:1	c.535-113241T>C		intron	N/A	ENSP00000355863.1
	PRKN	ENST00000366896.5	TSL:1	c.172-113241T>C		intron	N/A	ENSP00000355862.1

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116603 AN: 152022 Hom.: 45175 Cov.: 33

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.767 AC: 116702 AN: 152140 Hom.: 45220 Cov.: 33 AF XY: 0.768 AC XY: 57119 AN XY: 74372

African (AFR) AF: 0.883 AC: 36668 AN: 41522

American (AMR) AF: 0.733 AC: 11208 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2592 AN: 3472

East Asian (EAS) AF: 0.860 AC: 4442 AN: 5164

South Asian (SAS) AF: 0.717 AC: 3454 AN: 4820

European-Finnish (FIN) AF: 0.731 AC: 7730 AN: 10572

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48053 AN: 67988

Other (OTH) AF: 0.751 AC: 1585 AN: 2110

Alfa AF: 0.729 Hom.: 116231

Bravo AF: 0.775

Asia WGS AF: 0.814 AC: 2828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.14
DANN	Benign	0.52
PhyloP100		-1.2
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: rs1893551; hg19: chr6-162507690;