rs9456734

Variant names:

• chr6-162053861-A-G
• rs9456734
• NM_004562.3:c.618+230T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-162053861-A-G
• chr6-162053861-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004562.3(PRKN):​c.618+230T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,118 control chromosomes in the GnomAD database, including 3,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3379 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0220
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-162053861-A-G is Benign according to our data. Variant chr6-162053861-A-G is described in ClinVar as Benign. ClinVar VariationId is 1228283.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.618+230T>C		intron_variant	Intron 5 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.618+230T>C		intron_variant	Intron 5 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29533 AN: 152000 Hom.: 3372 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.194 AC: 29559 AN: 152118 Hom.: 3379 Cov.: 32 AF XY: 0.200 AC XY: 14867 AN XY: 74354

African (AFR) AF: 0.154 AC: 6387 AN: 41490

American (AMR) AF: 0.235 AC: 3596 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 793 AN: 3472

East Asian (EAS) AF: 0.552 AC: 2854 AN: 5168

South Asian (SAS) AF: 0.234 AC: 1129 AN: 4816

European-Finnish (FIN) AF: 0.235 AC: 2489 AN: 10572

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11809 AN: 68002

Other (OTH) AF: 0.183 AC: 386 AN: 2112

Alfa AF: 0.174 Hom.: 4060

Bravo AF: 0.197

Asia WGS AF: 0.389 AC: 1353 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.43
PhyloP100		0.022
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9456734; hg19: chr6-162474893; COSMIC: COSV58267357;