6-163314914-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080379.2(PACRG):​c.701G>T​(p.Arg234Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PACRG
NM_001080379.2 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.58
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-AS1 (HGNC:27772): (PACRG antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PACRGNM_001080379.2 linkc.701G>T p.Arg234Leu missense_variant Exon 5 of 5 ENST00000366888.7 NP_001073848.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PACRGENST00000366888.7 linkc.701G>T p.Arg234Leu missense_variant Exon 5 of 5 1 NM_001080379.2 ENSP00000355854.2 Q96M98-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251434
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461852
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.818G>T (p.R273L) alteration is located in exon 7 (coding exon 6) of the PACRG gene. This alteration results from a G to T substitution at nucleotide position 818, causing the arginine (R) at amino acid position 273 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
0.020
CADD
Benign
22
DANN
Benign
0.88
DEOGEN2
Benign
0.36
T;.;.;T
Eigen
Benign
0.076
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.96
D;.;D;D
M_CAP
Benign
0.015
T
MetaRNN
Uncertain
0.49
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;.;.;.
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-3.2
D;D;D;.
REVEL
Uncertain
0.30
Sift
Benign
0.28
T;T;T;.
Sift4G
Benign
0.60
T;T;T;T
Polyphen
0.027
B;B;B;.
Vest4
0.69
MutPred
0.55
Gain of catalytic residue at R273 (P = 0.0414);.;.;.;
MVP
0.68
MPC
0.36
ClinPred
0.69
D
GERP RS
5.9
Varity_R
0.55
gMVP
0.71

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.

Other links and lift over

dbSNP: rs199844557; hg19: chr6-163735946; API