6-161719955-A-G

Variant names:

• chr6-161719955-A-G
• rs10945770
• NM_004562.3:c.871+65817T>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.871+65817T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,130 control chromosomes in the GnomAD database, including 5,750 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 0.22 (5750 hom., cov: 33)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 5 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 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+65817T>C		intron	N/A	NP_004553.2
	PRKN	NM_013987.3		c.787+65817T>C		intron	N/A	NP_054642.2
	PRKN	NM_013988.3		c.424+65817T>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.871+65817T>C		intron	N/A	ENSP00000355865.1
	PRKN	ENST00000366897.5	TSL:1	c.787+65817T>C		intron	N/A	ENSP00000355863.1
	PRKN	ENST00000366896.5	TSL:1	c.424+65817T>C		intron	N/A	ENSP00000355862.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32891 AN: 152012 Hom.: 5723 Cov.: 33

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0847

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.217 AC: 32965 AN: 152130 Hom.: 5750 Cov.: 33 AF XY: 0.209 AC XY: 15569 AN XY: 74382

African (AFR) AF: 0.485 AC: 20088 AN: 41450

American (AMR) AF: 0.108 AC: 1657 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 404 AN: 3470

East Asian (EAS) AF: 0.0417 AC: 215 AN: 5158

South Asian (SAS) AF: 0.125 AC: 604 AN: 4832

European-Finnish (FIN) AF: 0.0847 AC: 898 AN: 10600

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8579 AN: 68012

Other (OTH) AF: 0.177 AC: 372 AN: 2106

Alfa AF: 0.137 Hom.: 3426

Bravo AF: 0.228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.31
PhyloP100		-0.35
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: rs10945770; hg19: chr6-162140987;