Variant 10-116436825-G-A 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_001011709.3(PNLIPRP3):c.164G>A(p.Arg55His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,612,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

PNLIPRP3
NM_001011709.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

Variant links:

Genes affected

PNLIPRP3 (HGNC:23492): (pancreatic lipase related protein 3) Predicted to enable triglyceride lipase activity. Predicted to be involved in lipid catabolic process. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

PNLIPRP3 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=0.17294821).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PNLIPRP3	NM_001011709.3 linkuse as main transcript	c.164G>A	p.Arg55His	missense_variant	2/12	ENST00000369230.4
PNLIPRP3	XM_011539276.2 linkuse as main transcript	c.164G>A	p.Arg55His	missense_variant	2/10
PNLIPRP3	XM_011539278.1 linkuse as main transcript	c.-283G>A		5_prime_UTR_variant	1/12
PNLIPRP3	XM_011539279.2 linkuse as main transcript	c.-111-6230G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNLIPRP3	ENST00000369230.4 linkuse as main transcript	c.164G>A	p.Arg55His	missense_variant	2/12	1	NM_001011709.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

151906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000532

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000837

AC:

AN:

250966

Hom.:

AF XY:

0.0000811

AC XY:

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.000862

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461036

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

726848

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000151

AC:

AN:

151906

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74190

show subpopulations

Gnomad4 AFR

AF:

0.000532

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000175

Hom.:

Bravo

AF:

0.000208

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

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

Mar 18, 2024

The c.164G>A (p.R55H) alteration is located in exon 2 (coding exon 2) of the PNLIPRP3 gene. This alteration results from a G to A substitution at nucleotide position 164, causing the arginine (R) at amino acid position 55 to be replaced by a histidine (H). 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

0.084

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.29

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.017

MetaRNN

Benign

0.17

MetaSVM

Uncertain

0.36

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.81

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.46

Sift

Benign

0.069

Sift4G

Uncertain

0.049

Polyphen

0.94

Vest4

0.43

MVP

0.89

MPC

0.14

ClinPred

0.079

GERP RS

4.6

Varity_R

0.18

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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