chr6-163314984-C-T

Variant names:

• chr6-163314984-C-T
• rs60454188
• NM_001080379.2:c.771C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001080379.2(PACRG):​c.771C>T​(p.Asn257Asn) variant causes a synonymous change. The variant allele was found at a frequency of 0.00298 in 1,612,908 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (64 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (52 hom.)
• Consequence: PACRG NM_001080379.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.11
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 6-163314984-C-T is Benign according to our data. Variant chr6-163314984-C-T is described in ClinVar as Benign. ClinVar VariationId is 792063.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

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.771C>T	p.Asn257Asn	synonymous	Exon 5 of 5	NP_001073848.1	Q96M98-2
	PACRG	NM_152410.3		c.888C>T	p.Asn296Asn	synonymous	Exon 7 of 7	NP_689623.2	Q96M98-1
	PACRG	NM_001080378.2		c.771C>T	p.Asn257Asn	synonymous	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.771C>T	p.Asn257Asn	synonymous	Exon 5 of 5	ENSP00000355854.2	Q96M98-2
	PACRG	ENST00000366889.6	TSL:1	c.771C>T	p.Asn257Asn	synonymous	Exon 6 of 6	ENSP00000355855.2	Q96M98-2
	PACRG	ENST00000337019.7	TSL:2	c.888C>T	p.Asn296Asn	synonymous	Exon 7 of 7	ENSP00000337946.3	Q96M98-1

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2432 AN: 152172 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00390 AC: 976 AN: 250068 AF XY: 0.00294

Gnomad AFR exome AF: 0.0522

Gnomad AMR exome AF: 0.00259

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000248

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00162 AC: 2369 AN: 1460618 Hom.: 52 Cov.: 30 AF XY: 0.00133 AC XY: 968 AN XY: 726510

African (AFR) AF: 0.0548 AC: 1833 AN: 33442

American (AMR) AF: 0.00287 AC: 128 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39672

South Asian (SAS) AF: 0.0000465 AC: 4 AN: 86076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5756

European-Non Finnish (NFE) AF: 0.000164 AC: 182 AN: 1111290

Other (OTH) AF: 0.00335 AC: 202 AN: 60338

GnomAD4 genome AF: 0.0160 AC: 2434 AN: 152290 Hom.: 64 Cov.: 32 AF XY: 0.0157 AC XY: 1170 AN XY: 74470

African (AFR) AF: 0.0553 AC: 2298 AN: 41540

American (AMR) AF: 0.00562 AC: 86 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68026

Other (OTH) AF: 0.0118 AC: 25 AN: 2112

Alfa AF: 0.00682 Hom.: 14

Bravo AF: 0.0179

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.0
DANN	Benign	0.50
PhyloP100		5.1
Mutation Taster		=28/72	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs60454188; hg19: chr6-163736016;