6-161934723-T-C

Variant names:

• chr6-161934723-T-C
• rs7746164
• NM_004562.3:c.734+38579A>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.734+38579A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,886 control chromosomes in the GnomAD database, including 23,658 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 0.56 (23658 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875
• Publications: 2 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: Genomics England PanelApp, Laboratory for Molecular Medicine
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 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.734+38579A>G		intron	N/A	NP_004553.2	O60260-1
	PRKN	NM_013987.3		c.650+38579A>G		intron	N/A	NP_054642.2	O60260-2
	PRKN	NM_013988.3		c.287+38579A>G		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.734+38579A>G		intron	N/A	ENSP00000355865.1	O60260-1
	PRKN	ENST00000366897.5	TSL:1	c.650+38579A>G		intron	N/A	ENSP00000355863.1	O60260-2
	PRKN	ENST00000366896.5	TSL:1	c.287+38579A>G		intron	N/A	ENSP00000355862.1	O60260-6

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84437 AN: 151768 Hom.: 23622 Cov.: 32

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.556 AC: 84518 AN: 151886 Hom.: 23658 Cov.: 32 AF XY: 0.559 AC XY: 41492 AN XY: 74214

African (AFR) AF: 0.620 AC: 25671 AN: 41390

American (AMR) AF: 0.498 AC: 7614 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1897 AN: 3468

East Asian (EAS) AF: 0.534 AC: 2747 AN: 5146

South Asian (SAS) AF: 0.538 AC: 2594 AN: 4818

European-Finnish (FIN) AF: 0.589 AC: 6206 AN: 10534

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

European-Non Finnish (NFE) AF: 0.527 AC: 35819 AN: 67948

Other (OTH) AF: 0.552 AC: 1162 AN: 2106

Alfa AF: 0.539 Hom.: 16792

Bravo AF: 0.549

Asia WGS AF: 0.518 AC: 1793 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.62
DANN	Benign	0.48
PhyloP100		-0.88
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: rs7746164; hg19: chr6-162355755;