chr6-162718148-T-G

Variant names:

• chr6-162718148-T-G
• rs2803104
• NM_004562.3:c.7+9514A>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.7+9514A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,848 control chromosomes in the GnomAD database, including 10,464 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 0.37 (10464 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378
• Publications: 1 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKN	NM_004562.3	MANE Select	c.7+9514A>C		intron	N/A	NP_004553.2	O60260-1
	PRKN	NM_013987.3		c.7+9514A>C		intron	N/A	NP_054642.2	O60260-2
	PRKN	NM_013988.3		c.7+9514A>C		intron	N/A	NP_054643.2	O60260-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKN	ENST00000366898.6	TSL:1 MANE Select	c.7+9514A>C		intron	N/A	ENSP00000355865.1	O60260-1
	PRKN	ENST00000366897.5	TSL:1	c.7+9514A>C		intron	N/A	ENSP00000355863.1	O60260-2
	PRKN	ENST00000366896.5	TSL:1	c.7+9514A>C		intron	N/A	ENSP00000355862.1	O60260-6

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55801 AN: 151730 Hom.: 10457 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.368 AC: 55836 AN: 151848 Hom.: 10464 Cov.: 32 AF XY: 0.360 AC XY: 26687 AN XY: 74212

African (AFR) AF: 0.334 AC: 13836 AN: 41396

American (AMR) AF: 0.355 AC: 5417 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1452 AN: 3466

East Asian (EAS) AF: 0.305 AC: 1570 AN: 5152

South Asian (SAS) AF: 0.181 AC: 874 AN: 4816

European-Finnish (FIN) AF: 0.356 AC: 3734 AN: 10494

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27782 AN: 67932

Other (OTH) AF: 0.387 AC: 816 AN: 2110

Alfa AF: 0.274 Hom.: 824

Bravo AF: 0.373

Asia WGS AF: 0.256 AC: 892 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.61
PhyloP100		0.38
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: rs2803104; hg19: chr6-163139180; COSMIC: COSV58269986;