6-162790757-C-T

Variant names:

• chr6-162790757-C-T
• rs6915128
• NM_001080379.2:c.157-23390C>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.157-23390C>T 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 151,870 control chromosomes in the GnomAD database, including 23,277 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 (23277 hom., cov: 32)
• Consequence: PACRG NM_001080379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 3 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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 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.157-23390C>T		intron	N/A	NP_001073848.1	Q96M98-2
	PACRG	NM_152410.3		c.157-23390C>T		intron	N/A	NP_689623.2	Q96M98-1
	PACRG	NM_001080378.2		c.157-23390C>T		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.157-23390C>T		intron	N/A	ENSP00000355854.2	Q96M98-2
	PACRG	ENST00000366889.6	TSL:1	c.157-23390C>T		intron	N/A	ENSP00000355855.2	Q96M98-2
	PACRG	ENST00000337019.7	TSL:2	c.157-23390C>T		intron	N/A	ENSP00000337946.3	Q96M98-1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82577 AN: 151752 Hom.: 23255 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.544 AC: 82647 AN: 151870 Hom.: 23277 Cov.: 32 AF XY: 0.548 AC XY: 40670 AN XY: 74216

African (AFR) AF: 0.672 AC: 27819 AN: 41420

American (AMR) AF: 0.612 AC: 9334 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1542 AN: 3470

East Asian (EAS) AF: 0.664 AC: 3419 AN: 5146

South Asian (SAS) AF: 0.578 AC: 2778 AN: 4808

European-Finnish (FIN) AF: 0.417 AC: 4402 AN: 10548

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

European-Non Finnish (NFE) AF: 0.464 AC: 31497 AN: 67914

Other (OTH) AF: 0.536 AC: 1132 AN: 2110

Alfa AF: 0.353 Hom.: 918

Bravo AF: 0.563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.39
DANN	Benign	0.77
PhyloP100		-1.3
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: rs6915128; hg19: chr6-163211789; COSMIC: COSV61319713;