Variant 4-20704723-G-A details in Genebe, Genetics Data Aggregator

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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47

Variant links:

Genes affected

PACRGL (HGNC:28442): (parkin coregulated like)

PACRGL links:

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
PACRGL	NM_001258345.3 linkuse as main transcript	c.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
PACRGL	ENST00000503585.6 linkuse as main transcript	c.116G>A	p.Ser39Asn	missense_variant	3/9	2	NM_001258345.3	ENSP00000423881	P1	Q8N7B6-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

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:

AN:

251354

Hom.:

AF XY:

0.0000515

AC XY:

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:

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

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:

AN:

152168

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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:

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 submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The 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

BayesDel_noAF

Benign

-0.49

CADD

Benign

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

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

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

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

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

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.

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