dbSNP rs199982588: PAPLN:p.Arg102Gln (chr14-73246146-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001365906.3(PAPLN):c.305G>A(p.Arg102Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000239 in 1,591,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R102W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

PAPLN
NM_001365906.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.44

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:

PAPLN-AS1 (HGNC:55451): (PAPLN antisense RNA 1)

PAPLN-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04649082).

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.305G>A	p.Arg102Gln	missense	Exon 5 of 27	NP_001352835.1	O95428-1
PAPLN	NM_001365907.2		c.305G>A	p.Arg102Gln	missense	Exon 4 of 26	NP_001352836.1	O95428-5
PAPLN	NM_173462.4		c.305G>A	p.Arg102Gln	missense	Exon 5 of 26	NP_775733.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAPLN	ENST00000644200.2	MANE Select	c.305G>A	p.Arg102Gln	missense	Exon 5 of 27	ENSP00000495882.2	O95428-1
PAPLN	ENST00000216658.9	TSL:1	n.305G>A		non_coding_transcript_exon	Exon 5 of 27	ENSP00000216658.5	B5MDP7
PAPLN	ENST00000555123.5	TSL:1	n.305G>A		non_coding_transcript_exon	Exon 5 of 24	ENSP00000452455.1	G3V5P6

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000758

AC:

AN:

211154

AF XY:

0.0000600

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000222

AC:

AN:

1439186

Hom.:

Cov.:

AF XY:

0.0000196

AC XY:

AN XY:

715794

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30880

American (AMR)

AF:

0.00

AC:

AN:

41380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25198

East Asian (EAS)

AF:

0.000507

AC:

AN:

37468

South Asian (SAS)

AF:

0.00

AC:

AN:

83930

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51678

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00000997

AC:

AN:

1103670

Other (OTH)

AF:

0.0000337

AC:

AN:

59286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41562

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000913

AC:

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

0.099

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.49

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

Eigen

Benign

-0.014

Eigen_PC

Benign

-0.080

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0056

MetaRNN

Benign

0.046

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.6

PhyloP100

5.4

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.3

REVEL

Benign

0.18

Sift

Uncertain

0.021

Sift4G

Uncertain

0.056

Polyphen

0.97

Vest4

0.57

MVP

0.18

MPC

0.31

ClinPred

0.23

GERP RS

2.2

Varity_R

0.087

gMVP

0.38

Mutation Taster

=94/6

polymorphism

(source)

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over