6-163306965-G-C

Variant names:

• chr6-163306965-G-C
• rs742329
• NM_001080379.2:c.614-7862G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080379.2(PACRG):​c.614-7862G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,142 control chromosomes in the GnomAD database, including 2,920 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 0.18 (2920 hom., cov: 33)
• Consequence: PACRG NM_001080379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 0 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]

PACRG-AS1 (HGNC:27772): (PACRG antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PACRG	NM_001080379.2	c.614-7862G>C		intron_variant	Intron 4 of 4	ENST00000366888.7	NP_001073848.1
PACRG	NM_152410.3	c.614-5814G>C		intron_variant	Intron 5 of 6		NP_689623.2
PACRG	NM_001080378.2	c.614-7862G>C		intron_variant	Intron 5 of 5		NP_001073847.1
PACRG	XM_047418208.1	c.614-7862G>C		intron_variant	Intron 5 of 5		XP_047274164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PACRG	ENST00000366888.7	c.614-7862G>C		intron_variant	Intron 4 of 4	1	NM_001080379.2	ENSP00000355854.2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26718 AN: 152026 Hom.: 2914 Cov.: 33

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.176 AC: 26749 AN: 152142 Hom.: 2920 Cov.: 33 AF XY: 0.174 AC XY: 12967 AN XY: 74386

African (AFR) AF: 0.307 AC: 12720 AN: 41484

American (AMR) AF: 0.156 AC: 2391 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3470

East Asian (EAS) AF: 0.0313 AC: 162 AN: 5180

South Asian (SAS) AF: 0.164 AC: 787 AN: 4812

European-Finnish (FIN) AF: 0.128 AC: 1351 AN: 10584

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8320 AN: 68006

Other (OTH) AF: 0.156 AC: 330 AN: 2114

Alfa AF: 0.0541 Hom.: 62

Bravo AF: 0.182

Asia WGS AF: 0.114 AC: 399 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.56
DANN	Benign	0.50
PhyloP100		-0.30
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: rs742329; hg19: chr6-163727997;