chr6-162792995-A-G

Variant names:

• chr6-162792995-A-G
• rs1040079
• NM_001080379.2:c.157-21152A>G

Variant summary

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

The NM_001080379.2(PACRG):​c.157-21152A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,036 control chromosomes in the GnomAD database, including 8,111 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 0.31 (8111 hom., cov: 32)
• Consequence: PACRG NM_001080379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 18 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PACRG	NM_001080379.2	c.157-21152A>G		intron_variant	Intron 1 of 4	ENST00000366888.7	NP_001073848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PACRG	ENST00000366888.7	c.157-21152A>G		intron_variant	Intron 1 of 4	1	NM_001080379.2	ENSP00000355854.2

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47293 AN: 151918 Hom.: 8086 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.311 AC: 47359 AN: 152036 Hom.: 8111 Cov.: 32 AF XY: 0.308 AC XY: 22911 AN XY: 74322

African (AFR) AF: 0.419 AC: 17377 AN: 41434

American (AMR) AF: 0.432 AC: 6591 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1095 AN: 3470

East Asian (EAS) AF: 0.179 AC: 925 AN: 5160

South Asian (SAS) AF: 0.272 AC: 1310 AN: 4818

European-Finnish (FIN) AF: 0.134 AC: 1417 AN: 10588

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17614 AN: 67980

Other (OTH) AF: 0.326 AC: 687 AN: 2106

Alfa AF: 0.286 Hom.: 1354

Bravo AF: 0.337

Asia WGS AF: 0.275 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.71
PhyloP100		-0.087
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: rs1040079; hg19: chr6-163214027;