chr6-161575338-C-T

Variant names:

• chr6-161575338-C-T
• rs7755681
• NM_004562.3:c.872-5922G>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.872-5922G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 151,976 control chromosomes in the GnomAD database, including 31,290 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 0.64 (31290 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 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.872-5922G>A		intron	N/A	NP_004553.2
	PRKN	NM_013987.3		c.788-5922G>A		intron	N/A	NP_054642.2
	PRKN	NM_013988.3		c.425-5922G>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.872-5922G>A		intron	N/A	ENSP00000355865.1
	PRKN	ENST00000366897.5	TSL:1	c.788-5922G>A		intron	N/A	ENSP00000355863.1
	PRKN	ENST00000366896.5	TSL:1	c.425-5922G>A		intron	N/A	ENSP00000355862.1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96521 AN: 151858 Hom.: 31266 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.636 AC: 96594 AN: 151976 Hom.: 31290 Cov.: 32 AF XY: 0.636 AC XY: 47233 AN XY: 74280

African (AFR) AF: 0.760 AC: 31490 AN: 41460

American (AMR) AF: 0.517 AC: 7896 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2411 AN: 3472

East Asian (EAS) AF: 0.694 AC: 3580 AN: 5158

South Asian (SAS) AF: 0.552 AC: 2654 AN: 4810

European-Finnish (FIN) AF: 0.666 AC: 7027 AN: 10548

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39463 AN: 67954

Other (OTH) AF: 0.620 AC: 1308 AN: 2108

Alfa AF: 0.601 Hom.: 67214

Bravo AF: 0.628

Asia WGS AF: 0.612 AC: 2132 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		0.0060
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: rs7755681; hg19: chr6-161996370; COSMIC: COSV58266111;