chr4-20704723-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001258345.3(PACRGL):​c.116G>A​(p.Ser39Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

PACRGL
NM_001258345.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47
Variant links:
Genes affected
PACRGL (HGNC:28442): (parkin coregulated like)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.029059142).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PACRGLNM_001258345.3 linkuse as main transcriptc.116G>A p.Ser39Asn missense_variant 3/9 ENST00000503585.6 NP_001245274.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PACRGLENST00000503585.6 linkuse as main transcriptc.116G>A p.Ser39Asn missense_variant 3/92 NM_001258345.3 ENSP00000423881 P1Q8N7B6-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000796
AC:
20
AN:
251354
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135844
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00109
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:
0.00000958
AC:
14
AN:
1461762
Hom.:
0
Cov.:
34
AF XY:
0.00000550
AC XY:
4
AN XY:
727190
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000302
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ExAC
AF:
0.0000741
AC:
9

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 28, 2023The c.116G>A (p.S39N) alteration is located in exon 3 (coding exon 2) of the PACRGL gene. This alteration results from a G to A substitution at nucleotide position 116, causing the serine (S) at amino acid position 39 to be replaced by an asparagine (N). 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
0.070
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.026
T;T;.;.;.;.;T;T;.;.;T;.;.;.;.;.;.;T;T
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.48
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.65
T;T;.;.;T;T;T;T;T;T;T;T;T;T;T;T;.;T;T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.029
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
.;L;L;L;.;L;.;.;.;.;.;L;.;.;.;.;L;.;.
MutationTaster
Benign
0.99
N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.6
N;N;N;N;N;N;N;N;N;D;N;N;N;N;N;D;N;N;N
REVEL
Benign
0.099
Sift
Benign
0.030
D;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.099
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.034
B;B;B;B;.;.;.;.;.;.;.;.;.;.;.;.;B;B;.
Vest4
0.18, 0.22, 0.21, 0.26, 0.22, 0.22
MutPred
0.15
.;Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);Loss of phosphorylation at S39 (P = 0.0215);
MVP
0.014
MPC
0.065
ClinPred
0.080
T
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.073
gMVP
0.31

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: rs780926922; hg19: chr4-20706346; API