rs1333962

Variant names:

• chr6-162847872-T-C
• rs1333962
• NM_001080379.2:c.291+33591T>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.291+33591T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,938 control chromosomes in the GnomAD database, including 26,515 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 0.57 (26515 hom., cov: 31)
• Consequence: PACRG NM_001080379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.745
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PACRG	NM_001080379.2	c.291+33591T>C		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.291+33591T>C		intron_variant	Intron 2 of 4	1	NM_001080379.2	ENSP00000355854.2

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86211 AN: 151818 Hom.: 26458 Cov.: 31

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.568 AC: 86329 AN: 151938 Hom.: 26515 Cov.: 31 AF XY: 0.568 AC XY: 42190 AN XY: 74234

African (AFR) AF: 0.815 AC: 33808 AN: 41458

American (AMR) AF: 0.611 AC: 9316 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1677 AN: 3472

East Asian (EAS) AF: 0.584 AC: 3016 AN: 5164

South Asian (SAS) AF: 0.588 AC: 2828 AN: 4810

European-Finnish (FIN) AF: 0.409 AC: 4305 AN: 10536

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29704 AN: 67936

Other (OTH) AF: 0.546 AC: 1151 AN: 2108

Alfa AF: 0.491 Hom.: 14893

Bravo AF: 0.591

Asia WGS AF: 0.633 AC: 2198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.52
PhyloP100		-0.74
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: rs1333962; hg19: chr6-163268904;