Genetic Variant PNLIPRP1:p.Gly181Glu (chr10-116596290-G-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_006229.4(PNLIPRP1):c.542G>A(p.Gly181Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,390 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: 0.0000027 ( 0 hom. )

Consequence

PNLIPRP1
NM_006229.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.87

Publications

0 publications found

Variant links:

Genes affected

PNLIPRP1 (HGNC:9156): (pancreatic lipase related protein 1) Predicted to enable calcium ion binding activity. Predicted to be involved in lipid catabolic process. Predicted to be located in extracellular region. Biomarker of prostate cancer. [provided by Alliance of Genome Resources, Apr 2022]

PNLIPRP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.993

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNLIPRP1	NM_006229.4 link	c.542G>A	p.Gly181Glu	missense_variant	Exon 6 of 13	ENST00000358834.9	NP_006220.1	P54315-1
PNLIPRP1	NM_001303135.1 link	c.542G>A	p.Gly181Glu	missense_variant	Exon 6 of 13		NP_001290064.1	P54315-1
PNLIPRP1	XM_047425364.1 link	c.542G>A	p.Gly181Glu	missense_variant	Exon 6 of 9		XP_047281320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNLIPRP1	ENST00000358834.9 link	c.542G>A	p.Gly181Glu	missense_variant	Exon 6 of 13	1	NM_006229.4	ENSP00000351695.4		P54315-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251286

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461390

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727032

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111560

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 21, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.542G>A (p.G181E) alteration is located in exon 6 (coding exon 5) of the PNLIPRP1 gene. This alteration results from a G to A substitution at nucleotide position 542, causing the glycine (G) at amino acid position 181 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

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.54

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.88

D;D;D;.;.

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

D;.;D;D;D

M_CAP

Pathogenic

0.54

MetaRNN

Pathogenic

0.99

D;D;D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

4.5

.;H;H;.;.

PhyloP100

6.9

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-7.5

D;D;D;D;D

REVEL

Pathogenic

0.95

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

1.0

.;D;D;.;.

Vest4

0.96, 0.96

MutPred

0.95

Loss of catalytic residue at A180 (P = 0.0281);Loss of catalytic residue at A180 (P = 0.0281);Loss of catalytic residue at A180 (P = 0.0281);.;Loss of catalytic residue at A180 (P = 0.0281);

MVP

1.0

MPC

0.32

ClinPred

1.0

GERP RS

4.2

Varity_R

0.97

gMVP

0.96

Mutation Taster

=57/43

polymorphism

(source)

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

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10-116596290-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over