Genetic Variant PACRG:c.-244T>C (chr6-162727992-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0960

Variant links:

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 links:

PRKN (HGNC:8607): (parkin RBR E3 ubiquitin protein ligase) The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice variants of this gene have been described but currently lack transcript support. [provided by RefSeq, Jul 2008]

PRKN links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
PACRG	NM_001080379.2 link	c.-244T>C		5_prime_UTR_variant	Exon 1 of 5	ENST00000366888.7	NP_001073848.1
PRKN	NM_004562.3 link	c.-324A>G		upstream_gene_variant		ENST00000366898.6	NP_004553.2	O60260-1X5DR79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PACRG	ENST00000366888 link	c.-244T>C		5_prime_UTR_variant	Exon 1 of 5	1	NM_001080379.2	ENSP00000355854.2		Q96M98-2
PRKN	ENST00000366898.6 link	c.-324A>G		upstream_gene_variant		1	NM_004562.3	ENSP00000355865.1		O60260-1

Frequencies

GnomAD3 genomes

AF:

0.0859

AC:

13049

AN:

151964

Hom.:

696

Cov.:

show subpopulations

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.:

AF XY:

0.0986

AC XY:

24178

AN XY:

245154

show subpopulations

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.:

AF XY:

0.0831

AC XY:

6180

AN XY:

74332

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over