rs9347683

chr6-162728023-A-Cchr6-162728023-A-Gchr6-162728023-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080379.2(PACRG):c.-213A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 663,176 control chromosomes in the GnomAD database, including 19,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3216 hom., cov: 32)
  • Exomes 𝑓: 0.24 (16182 hom.)
• Consequence: PACRG NM_001080379.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.532

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 6-162728023-A-C is Benign according to our data. Variant chr6-162728023-A-C is described in ClinVar as [Benign]. Clinvar id is 1167504.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PACRG	NM_001080379.2	c.-213A>C		5_prime_UTR_variant	1/5	ENST00000366888.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PACRG	ENST00000366888.7	c.-213A>C		5_prime_UTR_variant	1/5	1	NM_001080379.2	P1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27630 AN: 151752 Hom.: 3215 Cov.: 32

Gnomad AFR AF: 0.0542

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.237 AC: 121003 AN: 511306 Hom.: 16182 Cov.: 6 AF XY: 0.239 AC XY: 64870 AN XY: 270938

Gnomad4 AFR exome AF: 0.0536

Gnomad4 AMR exome AF: 0.170

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.291

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.216

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.182 AC: 27627 AN: 151870 Hom.: 3216 Cov.: 32 AF XY: 0.190 AC XY: 14125 AN XY: 74214

Gnomad4 AFR AF: 0.0541

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.177

Alfa AF: 0.139 Hom.: 514

Bravo AF: 0.167

Asia WGS AF: 0.320 AC: 1114 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	0.79
Dann	Benign	0.86

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: rs9347683; hg19: chr6-163149055; COSMIC: COSV58217893; COSMIC: COSV58217893;