rs3016563

Variant names:

• chr6-161771824-C-A
• rs3016563
• NM_004562.3:c.871+13948G>T

Variant summary

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

The NM_004562.3(PRKN):​c.871+13948G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,940 control chromosomes in the GnomAD database, including 17,578 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 0.44 (17578 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 4 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=-0.55).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 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.871+13948G>T		intron	N/A	NP_004553.2
	PRKN	NM_013987.3		c.787+13948G>T		intron	N/A	NP_054642.2
	PRKN	NM_013988.3		c.424+13948G>T		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.871+13948G>T		intron	N/A	ENSP00000355865.1
	PRKN	ENST00000366897.5	TSL:1	c.787+13948G>T		intron	N/A	ENSP00000355863.1
	PRKN	ENST00000366896.5	TSL:1	c.424+13948G>T		intron	N/A	ENSP00000355862.1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67447 AN: 151822 Hom.: 17586 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.444 AC: 67430 AN: 151940 Hom.: 17578 Cov.: 32 AF XY: 0.450 AC XY: 33383 AN XY: 74226

African (AFR) AF: 0.156 AC: 6464 AN: 41434

American (AMR) AF: 0.476 AC: 7271 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1738 AN: 3466

East Asian (EAS) AF: 0.558 AC: 2884 AN: 5166

South Asian (SAS) AF: 0.401 AC: 1928 AN: 4808

European-Finnish (FIN) AF: 0.666 AC: 7026 AN: 10542

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.568 AC: 38581 AN: 67948

Other (OTH) AF: 0.470 AC: 994 AN: 2114

Alfa AF: 0.522 Hom.: 72919

Bravo AF: 0.423

Asia WGS AF: 0.440 AC: 1532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.72
PhyloP100		1.4
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: rs3016563; hg19: chr6-162192856;