rs6902041

Variant names:

• chr6-162427897-G-A
• rs6902041
• NM_004562.3:c.171+15413C>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.171+15413C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,878 control chromosomes in the GnomAD database, including 11,946 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 0.39 (11946 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 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.171+15413C>T		intron	N/A	NP_004553.2
	PRKN	NM_013987.3		c.171+15413C>T		intron	N/A	NP_054642.2
	PRKN	NM_013988.3		c.171+15413C>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.171+15413C>T		intron	N/A	ENSP00000355865.1
	PRKN	ENST00000366897.5	TSL:1	c.171+15413C>T		intron	N/A	ENSP00000355863.1
	PRKN	ENST00000366896.5	TSL:1	c.171+15413C>T		intron	N/A	ENSP00000355862.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59685 AN: 151760 Hom.: 11931 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.393 AC: 59734 AN: 151878 Hom.: 11946 Cov.: 32 AF XY: 0.398 AC XY: 29522 AN XY: 74208

African (AFR) AF: 0.338 AC: 13982 AN: 41402

American (AMR) AF: 0.429 AC: 6555 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1467 AN: 3468

East Asian (EAS) AF: 0.576 AC: 2963 AN: 5142

South Asian (SAS) AF: 0.401 AC: 1925 AN: 4804

European-Finnish (FIN) AF: 0.496 AC: 5230 AN: 10544

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26210 AN: 67936

Other (OTH) AF: 0.422 AC: 890 AN: 2110

Alfa AF: 0.396 Hom.: 2094

Bravo AF: 0.391

Asia WGS AF: 0.495 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.72
PhyloP100		0.17
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: rs6902041; hg19: chr6-162848929;