6-163016643-G-T

Variant names:

• chr6-163016643-G-T
• rs9356092
• NM_001080379.2:c.292-45507G>T

Variant summary

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

The NM_001080379.2(PACRG):​c.292-45507G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,762 control chromosomes in the GnomAD database, including 17,133 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 0.46 (17133 hom., cov: 31)
• Consequence: PACRG NM_001080379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 1 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PACRG	NM_001080379.2	c.292-45507G>T		intron_variant	Intron 2 of 4	ENST00000366888.7	NP_001073848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PACRG	ENST00000366888.7	c.292-45507G>T		intron_variant	Intron 2 of 4	1	NM_001080379.2	ENSP00000355854.2

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70109 AN: 151646 Hom.: 17113 Cov.: 31

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.462 AC: 70177 AN: 151762 Hom.: 17133 Cov.: 31 AF XY: 0.469 AC XY: 34767 AN XY: 74160

African (AFR) AF: 0.594 AC: 24604 AN: 41406

American (AMR) AF: 0.459 AC: 7004 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1391 AN: 3460

East Asian (EAS) AF: 0.718 AC: 3695 AN: 5144

South Asian (SAS) AF: 0.512 AC: 2468 AN: 4822

European-Finnish (FIN) AF: 0.434 AC: 4546 AN: 10466

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.369 AC: 25023 AN: 67900

Other (OTH) AF: 0.437 AC: 921 AN: 2106

Alfa AF: 0.355 Hom.: 1979

Bravo AF: 0.470

Asia WGS AF: 0.607 AC: 2103 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.40
PhyloP100		-1.4
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: rs9356092; hg19: chr6-163437675;