Genetic Variant PNLIPRP1:p.Gly35Val (chr10-116591825-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006229.4(PNLIPRP1):c.104G>T(p.Gly35Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G35D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PNLIPRP1
NM_006229.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.88

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNLIPRP1	NM_006229.4 link	c.104G>T	p.Gly35Val	missense_variant	Exon 3 of 13	ENST00000358834.9	NP_006220.1	P54315-1
PNLIPRP1	NM_001303135.1 link	c.104G>T	p.Gly35Val	missense_variant	Exon 3 of 13		NP_001290064.1	P54315-1
PNLIPRP1	XM_047425364.1 link	c.104G>T	p.Gly35Val	missense_variant	Exon 3 of 9		XP_047281320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNLIPRP1	ENST00000358834.9 link	c.104G>T	p.Gly35Val	missense_variant	Exon 3 of 13	1	NM_006229.4	ENSP00000351695.4		P54315-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251138

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

0.0073

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.49

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

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.085

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.63

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

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.47

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

MetaSVM

Uncertain

0.67

MutationAssessor

Benign

1.6

.;L;L;.;.;.;.

PhyloP100

1.9

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.8

D;D;D;D;D;D;D

REVEL

Uncertain

0.52

Sift

Uncertain

0.029

D;D;D;T;D;D;D

Sift4G

Benign

0.38

T;D;D;T;T;D;D

Polyphen

0.68

.;P;P;.;.;.;.

Vest4

0.33, 0.33, 0.33

MutPred

0.68

Loss of disorder (P = 0.1148);Loss of disorder (P = 0.1148);Loss of disorder (P = 0.1148);Loss of disorder (P = 0.1148);Loss of disorder (P = 0.1148);Loss of disorder (P = 0.1148);Loss of disorder (P = 0.1148);

MVP

0.95

MPC

0.15

ClinPred

0.83

GERP RS

2.4

Varity_R

0.46

gMVP

0.59

Mutation Taster

=75/25

polymorphism

(source)

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

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10-116591825-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over