Genetic Variant NM_006229.4:c.254T>G (chr10-116592465-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006229.4(PNLIPRP1):c.254T>G(p.Met85Arg) 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 1,461,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 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. M85T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PNLIPRP1
NM_006229.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.936

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.096174955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNLIPRP1	NM_006229.4 link	c.254T>G	p.Met85Arg	missense_variant	Exon 4 of 13	ENST00000358834.9	NP_006220.1	P54315-1
PNLIPRP1	NM_001303135.1 link	c.254T>G	p.Met85Arg	missense_variant	Exon 4 of 13		NP_001290064.1	P54315-1
PNLIPRP1	XM_047425364.1 link	c.254T>G	p.Met85Arg	missense_variant	Exon 4 of 9		XP_047281320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNLIPRP1	ENST00000358834.9 link	c.254T>G	p.Met85Arg	missense_variant	Exon 4 of 13	1	NM_006229.4	ENSP00000351695.4		P54315-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461316

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726854

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111666

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.30

CADD

Benign

0.83

(source)

DANN

Benign

0.29

DEOGEN2

Benign

0.34

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

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.096

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

M_CAP

Benign

0.061

MetaRNN

Benign

0.096

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

MetaSVM

Benign

-0.56

MutationAssessor

Benign

-0.57

.;N;N;.;.;.;.

PhyloP100

-0.94

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.2

N;N;N;N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.18

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

Sift4G

Benign

0.55

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

Polyphen

0.0020

.;B;B;.;.;.;.

Vest4

0.23, 0.24, 0.23

MutPred

0.48

Gain of disorder (P = 0.0371);Gain of disorder (P = 0.0371);Gain of disorder (P = 0.0371);Gain of disorder (P = 0.0371);Gain of disorder (P = 0.0371);Gain of disorder (P = 0.0371);Gain of disorder (P = 0.0371);

MVP

0.76

MPC

0.053

ClinPred

0.14

GERP RS

1.7

Varity_R

0.33

gMVP

0.44

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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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NM_006229.4:c.254T>G

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