6-162727992-T-C

Position:

• chr6-162727992-T-C

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.-244T>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 0.0951 in 616,736 control chromosomes in the GnomAD database, including 3,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.086 (698 hom., cov: 32)
  • Exomes 𝑓: 0.098 (2718 hom.)
• Consequence: PACRG NM_001080379.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0960

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=-0.65).
• BP6: Variant 6-162727992-T-C is Benign according to our data. Variant chr6-162727992-T-C is described in ClinVar as [Benign]. Clinvar id is 1270795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PACRG	NM_001080379.2	c.-244T>C		5_prime_UTR_variant	1/5	ENST00000366888.7	NP_001073848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PACRG	ENST00000366888.7	c.-244T>C		5_prime_UTR_variant	1/5	1	NM_001080379.2	ENSP00000355854	P1

Frequencies

GnomAD3 genomes AF: 0.0859 AC: 13049 AN: 151964 Hom.: 696 Cov.: 32

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0936

Gnomad ASJ AF: 0.0986

Gnomad EAS AF: 0.00156

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0981 AC: 45598 AN: 464654 Hom.: 2718 Cov.: 5 AF XY: 0.0986 AC XY: 24178 AN XY: 245154

Gnomad4 AFR exome AF: 0.0536

Gnomad4 AMR exome AF: 0.0713

Gnomad4 ASJ exome AF: 0.0893

Gnomad4 EAS exome AF: 0.000381

Gnomad4 SAS exome AF: 0.0976

Gnomad4 FIN exome AF: 0.0590

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.0858 AC: 13054 AN: 152082 Hom.: 698 Cov.: 32 AF XY: 0.0831 AC XY: 6180 AN XY: 74332

Gnomad4 AFR AF: 0.0507

Gnomad4 AMR AF: 0.0934

Gnomad4 ASJ AF: 0.0986

Gnomad4 EAS AF: 0.00156

Gnomad4 SAS AF: 0.0860

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0712 Hom.: 131

Bravo AF: 0.0874

Asia WGS AF: 0.0570 AC: 197 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

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs68144677; hg19: chr6-163149024;