rs13218900

Variant names:

• chr6-162660606-T-C
• rs13218900
• NM_004562.3:c.7+67056A>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.7+67056A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0876 in 152,246 control chromosomes in the GnomAD database, including 724 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 0.088 (724 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• 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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.7+67056A>G		intron_variant	Intron 1 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.7+67056A>G		intron_variant	Intron 1 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.0876 AC: 13332 AN: 152128 Hom.: 722 Cov.: 32

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.0937

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0874

Gnomad FIN AF: 0.0558

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.0876 AC: 13337 AN: 152246 Hom.: 724 Cov.: 32 AF XY: 0.0853 AC XY: 6348 AN XY: 74434

African (AFR) AF: 0.0533 AC: 2214 AN: 41564

American (AMR) AF: 0.0935 AC: 1429 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0905 AC: 314 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.0877 AC: 423 AN: 4824

European-Finnish (FIN) AF: 0.0558 AC: 592 AN: 10616

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.116 AC: 7918 AN: 67996

Other (OTH) AF: 0.111 AC: 235 AN: 2110

Alfa AF: 0.0876 Hom.: 95

Bravo AF: 0.0888

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		-0.18
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: rs13218900; hg19: chr6-163081638;