rs766673660

Variant names:

• chr6-162728252-A-G
• rs766673660
• NM_001080379.2:c.17A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080379.2(PACRG):​c.17A>G​(p.Glu6Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000694 in 1,613,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: PACRG NM_001080379.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1521542).

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.17A>G	p.Glu6Gly	missense	Exon 1 of 5	NP_001073848.1	Q96M98-2
	PACRG	NM_152410.3		c.17A>G	p.Glu6Gly	missense	Exon 2 of 7	NP_689623.2	Q96M98-1
	PACRG	NM_001080378.2		c.17A>G	p.Glu6Gly	missense	Exon 2 of 6	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.17A>G	p.Glu6Gly	missense	Exon 1 of 5	ENSP00000355854.2	Q96M98-2
	PACRG	ENST00000366889.6	TSL:1	c.17A>G	p.Glu6Gly	missense	Exon 2 of 6	ENSP00000355855.2	Q96M98-2
	PACRG	ENST00000337019.7	TSL:2	c.17A>G	p.Glu6Gly	missense	Exon 2 of 7	ENSP00000337946.3	Q96M98-1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000558 AC: 14 AN: 250698 AF XY: 0.0000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000467

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000746 AC: 109 AN: 1461338 Hom.: 0 Cov.: 31 AF XY: 0.0000674 AC XY: 49 AN XY: 726988

African (AFR) AF: 0.0000299 AC: 1 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000935 AC: 104 AN: 1111840

Other (OTH) AF: 0.0000663 AC: 4 AN: 60376

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74360

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000112 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000824 AC: 10

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.055
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		4.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.10
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.013	D
Polyphen		0.46	P
Vest4		0.43
MVP		0.71
MPC		0.37
ClinPred		0.33	T
GERP RS		5.3
PromoterAI		0.018	Neutral
Varity_R		0.16
gMVP		0.53
Mutation Taster		=81/19	polymorphism

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: rs766673660; hg19: chr6-163149284;