10-116436746-A-G

Variant summary

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

The NM_001011709.3(PNLIPRP3):​c.85A>G​(p.Lys29Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

PNLIPRP3
NM_001011709.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.805
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]

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=0.040299356).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PNLIPRP3NM_001011709.3 linkc.85A>G p.Lys29Glu missense_variant Exon 2 of 12 ENST00000369230.4 NP_001011709.2 Q17RR3
PNLIPRP3XM_011539276.2 linkc.85A>G p.Lys29Glu missense_variant Exon 2 of 10 XP_011537578.1
PNLIPRP3XM_011539279.2 linkc.-111-6309A>G intron_variant Intron 1 of 10 XP_011537581.1
PNLIPRP3XM_011539278.1 linkc.-362A>G upstream_gene_variant XP_011537580.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PNLIPRP3ENST00000369230.4 linkc.85A>G p.Lys29Glu missense_variant Exon 2 of 12 1 NM_001011709.3 ENSP00000358232.3 Q17RR3

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152188
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000359
AC:
9
AN:
250686
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135460
show subpopulations
Gnomad AFR exome
AF:
0.000554
Gnomad AMR exome
AF:
0.00
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:
0.0000157
AC:
23
AN:
1460986
Hom.:
0
Cov.:
31
AF XY:
0.0000151
AC XY:
11
AN XY:
726782
show subpopulations
Gnomad4 AFR exome
AF:
0.000568
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:
0.0000497
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152306
Hom.:
0
Cov.:
33
AF XY:
0.0000671
AC XY:
5
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.000240
Gnomad4 AMR
AF:
0.000131
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:
0.0000988
Hom.:
0
Bravo
AF:
0.000132
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 03, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.85A>G (p.K29E) alteration is located in exon 2 (coding exon 2) of the PNLIPRP3 gene. This alteration results from a A to G substitution at nucleotide position 85, causing the lysine (K) at amino acid position 29 to be replaced by a glutamic acid (E). 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
0.072
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
12
DANN
Benign
0.85
DEOGEN2
Benign
0.13
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.021
N
LIST_S2
Benign
0.18
T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.040
T
MetaSVM
Benign
-0.70
T
MutationAssessor
Benign
0.63
N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.45
N
REVEL
Benign
0.21
Sift
Benign
0.060
T
Sift4G
Benign
0.16
T
Polyphen
0.0020
B
Vest4
0.29
MVP
0.46
MPC
0.051
ClinPred
0.012
T
GERP RS
-6.2
Varity_R
0.058
gMVP
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs567727410; hg19: chr10-118196258; API