6-163314841-G-T

Variant names:

• chr6-163314841-G-T
• rs143276239
• NM_001080379.2:c.628G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001080379.2(PACRG):​c.628G>T​(p.Gly210Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G210S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PACRG NM_001080379.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.36
• 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]

PACRG-AS1 (HGNC:27772): (PACRG antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.763

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.628G>T	p.Gly210Cys	missense	Exon 5 of 5	NP_001073848.1	Q96M98-2
	PACRG	NM_152410.3		c.745G>T	p.Gly249Cys	missense	Exon 7 of 7	NP_689623.2	Q96M98-1
	PACRG	NM_001080378.2		c.628G>T	p.Gly210Cys	missense	Exon 6 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.628G>T	p.Gly210Cys	missense	Exon 5 of 5	ENSP00000355854.2	Q96M98-2
	PACRG	ENST00000366889.6	TSL:1	c.628G>T	p.Gly210Cys	missense	Exon 6 of 6	ENSP00000355855.2	Q96M98-2
	PACRG	ENST00000337019.7	TSL:2	c.745G>T	p.Gly249Cys	missense	Exon 7 of 7	ENSP00000337946.3	Q96M98-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461610 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727106

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111944

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.4
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.58		Loss of disorder (P = 0.021)
MVP		0.83
MPC		0.96
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.62
gMVP		0.67
Mutation Taster		=42/58	disease causing

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: rs143276239; hg19: chr6-163735873;