6-162792422-T-C

Variant names:

• chr6-162792422-T-C
• rs1333955
• NM_001080379.2:c.157-21725T>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.157-21725T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,860 control chromosomes in the GnomAD database, including 23,295 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 0.54 (23295 hom., cov: 31)
• Consequence: PACRG NM_001080379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575
• Publications: 16 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PACRG	NM_001080379.2	MANE Select	c.157-21725T>C		intron	N/A	NP_001073848.1
	PACRG	NM_152410.3		c.157-21725T>C		intron	N/A	NP_689623.2
	PACRG	NM_001080378.2		c.157-21725T>C		intron	N/A	NP_001073847.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PACRG	ENST00000366888.7	TSL:1 MANE Select	c.157-21725T>C		intron	N/A	ENSP00000355854.2
	PACRG	ENST00000366889.6	TSL:1	c.157-21725T>C		intron	N/A	ENSP00000355855.2
	PACRG	ENST00000337019.7	TSL:2	c.157-21725T>C		intron	N/A	ENSP00000337946.3

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82615 AN: 151742 Hom.: 23272 Cov.: 31

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.544 AC: 82684 AN: 151860 Hom.: 23295 Cov.: 31 AF XY: 0.548 AC XY: 40699 AN XY: 74202

African (AFR) AF: 0.671 AC: 27781 AN: 41396

American (AMR) AF: 0.613 AC: 9365 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1540 AN: 3462

East Asian (EAS) AF: 0.665 AC: 3427 AN: 5156

South Asian (SAS) AF: 0.578 AC: 2779 AN: 4808

European-Finnish (FIN) AF: 0.416 AC: 4382 AN: 10526

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31547 AN: 67926

Other (OTH) AF: 0.538 AC: 1137 AN: 2114

Alfa AF: 0.493 Hom.: 79116

Bravo AF: 0.564

Asia WGS AF: 0.615 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.70
PhyloP100		-0.57
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: rs1333955; hg19: chr6-163213454; COSMIC: COSV61300422;