10-116444470-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001011709.3(PNLIPRP3):​c.413G>A​(p.Arg138His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PNLIPRP3
NM_001011709.3 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PNLIPRP3NM_001011709.3 linkc.413G>A p.Arg138His missense_variant Exon 4 of 12 ENST00000369230.4 NP_001011709.2 Q17RR3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PNLIPRP3ENST00000369230.4 linkc.413G>A p.Arg138His missense_variant Exon 4 of 12 1 NM_001011709.3 ENSP00000358232.3 Q17RR3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461400
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727024
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.413G>A (p.R138H) alteration is located in exon 4 (coding exon 4) of the PNLIPRP3 gene. This alteration results from a G to A substitution at nucleotide position 413, causing the arginine (R) at amino acid position 138 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
0.16
BayesDel_addAF
Uncertain
0.092
D
BayesDel_noAF
Benign
-0.10
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.48
T
Eigen
Benign
-0.047
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.41
N
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.041
D
MetaRNN
Pathogenic
0.86
D
MetaSVM
Uncertain
0.17
D
MutationAssessor
Uncertain
2.6
M
PrimateAI
Benign
0.37
T
PROVEAN
Pathogenic
-4.7
D
REVEL
Uncertain
0.31
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.53
MutPred
0.74
Loss of methylation at R138 (P = 0.0284);
MVP
0.60
MPC
0.32
ClinPred
0.98
D
GERP RS
0.44
Varity_R
0.44
gMVP
0.57

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: rs1254572802; hg19: chr10-118203982; COSMIC: COSV65048755; COSMIC: COSV65048755; API