NM_004562.3:c.1083+67732A>G

Variant names:

• chr6-161481122-T-C
• rs2315314
• NM_004562.3:c.1083+67732A>G

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+67732A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 152,116 control chromosomes in the GnomAD database, including 17,771 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 0.46 (17771 hom., cov: 33)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.931
• 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

LOC105378098 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 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.1083+67732A>G		intron	N/A	NP_004553.2
	PRKN	NM_013987.3		c.999+67732A>G		intron	N/A	NP_054642.2
	PRKN	NM_013988.3		c.636+67732A>G		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.1083+67732A>G		intron	N/A	ENSP00000355865.1
	PRKN	ENST00000366897.5	TSL:1	c.999+67732A>G		intron	N/A	ENSP00000355863.1
	PRKN	ENST00000366896.5	TSL:1	c.636+67732A>G		intron	N/A	ENSP00000355862.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70133 AN: 151998 Hom.: 17776 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.461 AC: 70151 AN: 152116 Hom.: 17771 Cov.: 33 AF XY: 0.466 AC XY: 34653 AN XY: 74358

African (AFR) AF: 0.236 AC: 9799 AN: 41504

American (AMR) AF: 0.466 AC: 7124 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2364 AN: 3470

East Asian (EAS) AF: 0.539 AC: 2785 AN: 5166

South Asian (SAS) AF: 0.533 AC: 2568 AN: 4818

European-Finnish (FIN) AF: 0.560 AC: 5935 AN: 10596

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37705 AN: 67962

Other (OTH) AF: 0.494 AC: 1045 AN: 2114

Alfa AF: 0.521 Hom.: 15644

Bravo AF: 0.441

Asia WGS AF: 0.523 AC: 1821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.26
DANN	Benign	0.80
PhyloP100		-0.93
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: rs2315314; hg19: chr6-161902154; COSMIC: COSV58264687;