Genetic Variant PAPLN:p.Leu4Pro (chr14-73239789-T-C) – 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_001365906.3(PAPLN):c.11T>C(p.Leu4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PAPLN
NM_001365906.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

Publications

0 publications found

Variant links:

Genes affected

PAPLN (HGNC:19262): (papilin, proteoglycan like sulfated glycoprotein) Predicted to enable metalloendopeptidase activity. Predicted to be involved in extracellular matrix organization. Predicted to be located in basement membrane. Predicted to be active in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

PAPLN links:

Genome browser will be placed here

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=0.23719728).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365906.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAPLN	NM_001365906.3	MANE Select	c.11T>C	p.Leu4Pro	missense	Exon 2 of 27	NP_001352835.1	O95428-1
PAPLN	NM_001365907.2		c.11T>C	p.Leu4Pro	missense	Exon 1 of 26	NP_001352836.1	O95428-5
PAPLN	NM_173462.4		c.11T>C	p.Leu4Pro	missense	Exon 2 of 26	NP_775733.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAPLN	ENST00000644200.2	MANE Select	c.11T>C	p.Leu4Pro	missense	Exon 2 of 27	ENSP00000495882.2	O95428-1
PAPLN	ENST00000216658.9	TSL:1	n.11T>C		non_coding_transcript_exon	Exon 2 of 27	ENSP00000216658.5	B5MDP7
PAPLN	ENST00000555123.5	TSL:1	n.11T>C		non_coding_transcript_exon	Exon 2 of 24	ENSP00000452455.1	G3V5P6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000472

AC:

AN:

211972

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000303

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:

0.00000139

AC:

AN:

1441598

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

716578

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33258

American (AMR)

AF:

0.0000228

AC:

AN:

43890

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25882

East Asian (EAS)

AF:

0.00

AC:

AN:

39412

South Asian (SAS)

AF:

0.00

AC:

AN:

84490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5478

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108266

Other (OTH)

AF:

0.00

AC:

AN:

59838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.0063

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.011

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.36

M_CAP

Benign

0.050

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.65

PhyloP100

1.7

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.80

REVEL

Benign

0.25

Sift

Benign

0.044

Sift4G

Uncertain

0.0030

Polyphen

0.97

Vest4

0.48

MutPred

0.45

Gain of disorder (P = 0.0016)

MVP

0.41

MPC

0.31

ClinPred

0.33

GERP RS

3.2

PromoterAI

0.015

Neutral

(source)

Varity_R

0.49

gMVP

0.53

Mutation Taster

=80/20

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over