6-162792422-T-C

Variant names:

• chr6-162792422-T-C
• rs1333955
• NM_001080379.2:c.157-21725T>C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PACRG	NM_001080379.2	c.157-21725T>C		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.157-21725T>C		intron_variant	Intron 1 of 4	1	NM_001080379.2	ENSP00000355854.2

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

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.538

Alfa AF: 0.484 Hom.: 36771

Bravo AF: 0.564

Asia WGS AF: 0.615 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs1333955; hg19: chr6-163213454; COSMIC: COSV61300422;