Genetic Variant NM_001080379.2:c.-213A>C (chr6-162728023-A-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.-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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.532

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=-0.72).

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 rank	MANE	Protein	UniProt
PACRG	NM_001080379.2 link	c.-213A>C		5_prime_UTR_variant	Exon 1 of 5	ENST00000366888.7	NP_001073848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PACRG	ENST00000366888 link	c.-213A>C		5_prime_UTR_variant	Exon 1 of 5	1	NM_001080379.2	ENSP00000355854.2		Q96M98-2

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27630

AN:

151752

Hom.:

3215

Cov.:

show subpopulations

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.:

AF XY:

0.239

AC XY:

64870

AN XY:

270938

show subpopulations

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.:

AF XY:

0.190

AC XY:

14125

AN XY:

74214

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.72

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

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