Variant 14-73239789-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23719728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAPLN	NM_001365906.3 linkuse as main transcript	c.11T>C	p.Leu4Pro	missense_variant	2/27	ENST00000644200.2	NP_001352835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAPLN	ENST00000644200.2 linkuse as main transcript	c.11T>C	p.Leu4Pro	missense_variant	2/27		NM_001365906.3	ENSP00000495882	P1	O95428-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000472

AC:

AN:

211972

Hom.:

AF XY:

0.00

AC XY:

AN XY:

117554

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 02, 2023

The c.11T>C (p.L4P) alteration is located in exon 2 (coding exon 1) of the PAPLN gene. This alteration results from a T to C substitution at nucleotide position 11, causing the leucine (L) at amino acid position 4 to be replaced by a proline (P). 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

0.17

BayesDel_addAF

Benign

-0.0063

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.011

T;.;T;.

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.36

T;T;.;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.24

T;T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.65

N;N;N;N

MutationTaster

Benign

0.87

D;D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.80

.;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.044

.;D;D;D

Sift4G

Uncertain

0.0030

.;D;D;D

Polyphen

0.97

D;D;D;D

Vest4

0.48, 0.42, 0.43

MutPred

0.45

Gain of disorder (P = 0.0016);Gain of disorder (P = 0.0016);Gain of disorder (P = 0.0016);Gain of disorder (P = 0.0016);

MVP

0.41

MPC

0.31

ClinPred

0.33

GERP RS

3.2

Varity_R

0.49

gMVP

0.53

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over