Genetic Variant PACRG:p.Asn11Ser (chr6-162728267-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080379.2(PACRG):c.32A>G(p.Asn11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PACRG
NM_001080379.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.148

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05608955).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PACRG	NM_001080379.2	MANE Select	c.32A>G	p.Asn11Ser	missense	Exon 1 of 5	NP_001073848.1	Q96M98-2
PACRG	NM_152410.3		c.32A>G	p.Asn11Ser	missense	Exon 2 of 7	NP_689623.2	Q96M98-1
PACRG	NM_001080378.2		c.32A>G	p.Asn11Ser	missense	Exon 2 of 6	NP_001073847.1	Q96M98-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PACRG	ENST00000366888.7	TSL:1 MANE Select	c.32A>G	p.Asn11Ser	missense	Exon 1 of 5	ENSP00000355854.2	Q96M98-2
PACRG	ENST00000366889.6	TSL:1	c.32A>G	p.Asn11Ser	missense	Exon 2 of 6	ENSP00000355855.2	Q96M98-2
PACRG	ENST00000337019.7	TSL:2	c.32A>G	p.Asn11Ser	missense	Exon 2 of 7	ENSP00000337946.3	Q96M98-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.9

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.087

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.71

M_CAP

Benign

0.0036

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

PhyloP100

0.15

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.040

REVEL

Benign

0.14

Sift

Benign

0.17

Sift4G

Benign

0.24

Polyphen

0.0010

Vest4

0.14

MutPred

0.10

Gain of phosphorylation at N11 (P = 0.0367)

MVP

0.41

MPC

0.21

ClinPred

0.16

GERP RS

-1.5

PromoterAI

-0.0020

Neutral

(source)

Varity_R

0.064

gMVP

0.15

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over