rs9347683

Variant names:

• chr6-162728023-A-C
• rs9347683
• NM_001080379.2:c.-213A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-162728023-A-C
• chr6-162728023-A-G
• chr6-162728023-A-T

Variant summary

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

The NM_001080379.2(PACRG):​c.-213A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 663,176 control chromosomes in the GnomAD database, including 19,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3216 hom., cov: 32)
  • Exomes 𝑓: 0.24 (16182 hom.)
• Consequence: PACRG NM_001080379.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.532
• Publications: 20 publications found

Genes affected

PACRG (HGNC:19152): (parkin coregulated) This gene encodes a protein that is conserved across metazoans. In vertebrates, this gene is linked in a head-to-head arrangement with the adjacent parkin gene, which is associated with autosomal recessive juvenile Parkinson's disease. These genes are co-regulated in various tissues and they share a bi-directional promoter. Both genes are associated with susceptibility to leprosy. The parkin co-regulated gene protein forms a large molecular complex with chaperones, including heat shock proteins 70 and 90, and chaperonin components. This protein is also a component of Lewy bodies in Parkinson's disease patients, and it suppresses unfolded Pael receptor-induced neuronal cell death. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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=-0.72).
• BP6: Variant 6-162728023-A-C is Benign according to our data. Variant chr6-162728023-A-C is described in ClinVar as Benign. ClinVar VariationId is 1167504.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PACRG	NM_001080379.2	c.-213A>C		5_prime_UTR_variant	Exon 1 of 5	ENST00000366888.7	NP_001073848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PACRG	ENST00000366888.7	c.-213A>C		5_prime_UTR_variant	Exon 1 of 5	1	NM_001080379.2	ENSP00000355854.2

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27630 AN: 151752 Hom.: 3215 Cov.: 32

Gnomad AFR AF: 0.0542

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.237 AC: 121003 AN: 511306 Hom.: 16182 Cov.: 6 AF XY: 0.239 AC XY: 64870 AN XY: 270938

African (AFR) AF: 0.0536 AC: 747 AN: 13940

American (AMR) AF: 0.170 AC: 4048 AN: 23754

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 1809 AN: 14290

East Asian (EAS) AF: 0.481 AC: 16381 AN: 34022

South Asian (SAS) AF: 0.291 AC: 14486 AN: 49758

European-Finnish (FIN) AF: 0.287 AC: 9358 AN: 32612

Middle Eastern (MID) AF: 0.210 AC: 426 AN: 2030

European-Non Finnish (NFE) AF: 0.216 AC: 67640 AN: 312560

Other (OTH) AF: 0.216 AC: 6108 AN: 28340

GnomAD4 genome AF: 0.182 AC: 27627 AN: 151870 Hom.: 3216 Cov.: 32 AF XY: 0.190 AC XY: 14125 AN XY: 74214

African (AFR) AF: 0.0541 AC: 2243 AN: 41466

American (AMR) AF: 0.162 AC: 2479 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 451 AN: 3470

East Asian (EAS) AF: 0.477 AC: 2434 AN: 5100

South Asian (SAS) AF: 0.301 AC: 1446 AN: 4810

European-Finnish (FIN) AF: 0.303 AC: 3193 AN: 10554

Middle Eastern (MID) AF: 0.200 AC: 58 AN: 290

European-Non Finnish (NFE) AF: 0.215 AC: 14624 AN: 67882

Other (OTH) AF: 0.177 AC: 373 AN: 2108

Alfa AF: 0.117 Hom.: 537

Bravo AF: 0.167

Asia WGS AF: 0.320 AC: 1114 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.79
DANN	Benign	0.86
PhyloP100		-0.53
PromoterAI		-0.019	Neutral
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: rs9347683; hg19: chr6-163149055; COSMIC: COSV58217893; COSMIC: COSV58217893;