Variant rs17126352 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001365906.3(PAPLN):c.1327G>A(p.Val443Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,614,020 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0075 ( 17 hom., cov: 33)

Exomes 𝑓: 0.00075 ( 20 hom. )

Consequence

PAPLN
NM_001365906.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.671

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005782604).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00745 (1135/152316) while in subpopulation AFR AF= 0.0264 (1098/41570). AF 95% confidence interval is 0.0251. There are 17 homozygotes in gnomad4. There are 524 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAPLN	NM_001365906.3 linkuse as main transcript	c.1327G>A	p.Val443Ile	missense_variant	13/27	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.1327G>A	p.Val443Ile	missense_variant	13/27		NM_001365906.3	ENSP00000495882	P1	O95428-1

Frequencies

GnomAD3 genomes

AF:

0.00746

AC:

1135

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00186

AC:

467

AN:

251156

Hom.:

AF XY:

0.00139

AC XY:

189

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.0258

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000746

AC:

1091

AN:

1461704

Hom.:

Cov.:

AF XY:

0.000661

AC XY:

481

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.0271

Gnomad4 AMR exome

AF:

0.000917

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.00154

GnomAD4 genome

AF:

0.00745

AC:

1135

AN:

152316

Hom.:

Cov.:

AF XY:

0.00703

AC XY:

524

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0264

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00218

Hom.:

Bravo

AF:

0.00832

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0245

AC:

108

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00238

AC:

289

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.51

DANN

Benign

0.54

DEOGEN2

Benign

0.0044

T;.;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.083

T;T;.;T

MetaRNN

Benign

0.0058

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.43

N;.;N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.50

.;N;N;N

REVEL

Benign

0.010

Sift

Benign

0.51

.;T;T;T

Sift4G

Benign

0.44

.;T;T;T

Polyphen

0.0060

B;B;B;B

Vest4

0.063, 0.061

MVP

0.076

MPC

0.15

ClinPred

0.0016

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.023

gMVP

0.099

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over