chr6-163243780-T-G

Position:

• chr6-163243780-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080379.2(PACRG):​c.614-71047T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,190 control chromosomes in the GnomAD database, including 3,144 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 0.20 (3144 hom., cov: 33)
• Consequence: PACRG NM_001080379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PACRG	NM_001080379.2	c.614-71047T>G		intron_variant		ENST00000366888.7	NP_001073848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PACRG	ENST00000366888.7	c.614-71047T>G		intron_variant		1	NM_001080379.2	ENSP00000355854.2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30232 AN: 152072 Hom.: 3139 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.199 AC: 30250 AN: 152190 Hom.: 3144 Cov.: 33 AF XY: 0.201 AC XY: 14960 AN XY: 74414

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.219

Alfa AF: 0.198 Hom.: 1933

Bravo AF: 0.195

Asia WGS AF: 0.286 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.75

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: rs6904305; hg19: chr6-163664812;