chr6-161495216-C-T

Variant names:

• chr6-161495216-C-T
• rs10755582
• NM_004562.3:c.1083+53638G>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.1083+53638G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,052 control chromosomes in the GnomAD database, including 22,730 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 0.52 (22730 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 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.1083+53638G>A		intron	N/A	NP_004553.2	O60260-1
	PRKN	NM_013987.3		c.999+53638G>A		intron	N/A	NP_054642.2	O60260-2
	PRKN	NM_013988.3		c.636+53638G>A		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.1083+53638G>A		intron	N/A	ENSP00000355865.1	O60260-1
	PRKN	ENST00000366897.5	TSL:1	c.999+53638G>A		intron	N/A	ENSP00000355863.1	O60260-2
	PRKN	ENST00000366896.5	TSL:1	c.636+53638G>A		intron	N/A	ENSP00000355862.1	O60260-6

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78817 AN: 151934 Hom.: 22689 Cov.: 32

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.519 AC: 78912 AN: 152052 Hom.: 22730 Cov.: 32 AF XY: 0.508 AC XY: 37737 AN XY: 74300

African (AFR) AF: 0.774 AC: 32123 AN: 41492

American (AMR) AF: 0.416 AC: 6343 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1615 AN: 3472

East Asian (EAS) AF: 0.153 AC: 793 AN: 5176

South Asian (SAS) AF: 0.290 AC: 1394 AN: 4814

European-Finnish (FIN) AF: 0.389 AC: 4100 AN: 10550

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30991 AN: 67970

Other (OTH) AF: 0.507 AC: 1072 AN: 2116

Alfa AF: 0.481 Hom.: 3197

Bravo AF: 0.535

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.69
PhyloP100		-0.0090
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: rs10755582; hg19: chr6-161916248; COSMIC: COSV58264929;