chr6-162727992-T-C

Variant names:

• chr6-162727992-T-C
• rs68144677
• NM_001080379.2:c.-244T>C

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.-244T>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 0.0951 in 616,736 control chromosomes in the GnomAD database, including 3,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.086 (698 hom., cov: 32)
  • Exomes 𝑓: 0.098 (2718 hom.)
• Consequence: PACRG NM_001080379.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0960
• Publications: 10 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=-0.65).
• BP6: Variant 6-162727992-T-C is Benign according to our data. Variant chr6-162727992-T-C is described in ClinVar as Benign. ClinVar VariationId is 1270795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080379.2. 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
	PACRG	NM_001080379.2	MANE Select	c.-244T>C		5_prime_UTR	Exon 1 of 5	NP_001073848.1	Q96M98-2
	PACRG	NM_152410.3		c.-76-168T>C		intron	N/A	NP_689623.2	Q96M98-1
	PACRG	NM_001080378.2		c.-76-168T>C		intron	N/A	NP_001073847.1	Q96M98-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PACRG	ENST00000366888.7	TSL:1 MANE Select	c.-244T>C		5_prime_UTR	Exon 1 of 5	ENSP00000355854.2	Q96M98-2
	PACRG	ENST00000366889.6	TSL:1	c.-76-168T>C		intron	N/A	ENSP00000355855.2	Q96M98-2
	PACRG	ENST00000337019.7	TSL:2	c.-76-168T>C		intron	N/A	ENSP00000337946.3	Q96M98-1

Frequencies

GnomAD3 genomes AF: 0.0859 AC: 13049 AN: 151964 Hom.: 696 Cov.: 32

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0936

Gnomad ASJ AF: 0.0986

Gnomad EAS AF: 0.00156

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0981 AC: 45598 AN: 464654 Hom.: 2718 Cov.: 5 AF XY: 0.0986 AC XY: 24178 AN XY: 245154

African (AFR) AF: 0.0536 AC: 672 AN: 12526

American (AMR) AF: 0.0713 AC: 1354 AN: 19000

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 1224 AN: 13706

East Asian (EAS) AF: 0.000381 AC: 12 AN: 31536

South Asian (SAS) AF: 0.0976 AC: 4521 AN: 46320

European-Finnish (FIN) AF: 0.0590 AC: 1834 AN: 31070

Middle Eastern (MID) AF: 0.144 AC: 282 AN: 1964

European-Non Finnish (NFE) AF: 0.117 AC: 33018 AN: 281942

Other (OTH) AF: 0.101 AC: 2681 AN: 26590

GnomAD4 genome AF: 0.0858 AC: 13054 AN: 152082 Hom.: 698 Cov.: 32 AF XY: 0.0831 AC XY: 6180 AN XY: 74332

African (AFR) AF: 0.0507 AC: 2102 AN: 41490

American (AMR) AF: 0.0934 AC: 1429 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0986 AC: 342 AN: 3468

East Asian (EAS) AF: 0.00156 AC: 8 AN: 5130

South Asian (SAS) AF: 0.0860 AC: 414 AN: 4816

European-Finnish (FIN) AF: 0.0515 AC: 545 AN: 10592

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.115 AC: 7791 AN: 67974

Other (OTH) AF: 0.112 AC: 236 AN: 2114

Alfa AF: 0.0712 Hom.: 132

Bravo AF: 0.0874

Asia WGS AF: 0.0570 AC: 197 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		0.096
PromoterAI		0.24	Neutral
Mutation Taster		=299/1	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: rs68144677; hg19: chr6-163149024;