Variant 4-20704492-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001258345.3(PACRGL):c.11C>T(p.Ser4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,613,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

PACRGL
NM_001258345.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08356464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PACRGL	NM_001258345.3 linkuse as main transcript	c.11C>T	p.Ser4Leu	missense_variant	2/9	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.11C>T	p.Ser4Leu	missense_variant	2/9	2	NM_001258345.3	ENSP00000423881	P1	Q8N7B6-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151822

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000756

AC:

AN:

251208

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000219

AC:

320

AN:

1461734

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

154

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000271

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000112

AC:

AN:

151822

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000831

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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

Jan 23, 2024

The c.11C>T (p.S4L) alteration is located in exon 2 (coding exon 1) of the PACRGL gene. This alteration results from a C to T substitution at nucleotide position 11, causing the serine (S) at amino acid position 4 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

0.088

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

T;T;.;.;.;.;T;T;.;.;T;.;.;.;.;.;.;.;T;T

Eigen

Benign

-0.070

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.95

D;D;.;.;D;D;D;D;D;D;D;D;.;D;D;D;D;.;D;D

M_CAP

Benign

0.0025

MetaRNN

Benign

0.084

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.2

.;M;M;M;.;M;.;.;.;.;.;M;.;.;.;.;.;M;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.9

N;N;N;N;N;D;D;N;N;D;N;N;D;D;N;D;D;N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0020

D;D;D;D;D;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;D;D;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D

Polyphen

0.89

P;P;P;P;.;.;.;.;.;.;.;.;.;.;.;.;.;P;B;.

Vest4

0.31, 0.34, 0.30, 0.31, 0.31, 0.30

MVP

0.067

MPC

0.087

ClinPred

0.12

GERP RS

6.2

Varity_R

0.10

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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