PAPLN p.Lys145Asn

Variant names:

• chr14-73250084-G-T
• NM_001365906.3:c.435G>T
• PAPLN p.Lys145Asn

Your query was ambiguous. Multiple possible variants found:

• chr14-73250084-G-T
• chr14-73250084-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365906.3(PAPLN):​c.435G>T​(p.Lys145Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PAPLN NM_001365906.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433
• Publications: 0 publications found

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]

ACMG classification

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=0.16059726).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPLN	NM_001365906.3	MANE Select	c.435G>T	p.Lys145Asn	missense	Exon 6 of 27	NP_001352835.1	O95428-1
	PAPLN	NM_001365907.2		c.435G>T	p.Lys145Asn	missense	Exon 5 of 26	NP_001352836.1	O95428-5
	PAPLN	NM_173462.4		c.435G>T	p.Lys145Asn	missense	Exon 6 of 26	NP_775733.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPLN	ENST00000644200.2	MANE Select	c.435G>T	p.Lys145Asn	missense	Exon 6 of 27	ENSP00000495882.2	O95428-1
	PAPLN	ENST00000216658.9	TSL:1	n.435G>T		non_coding_transcript_exon	Exon 6 of 27	ENSP00000216658.5	B5MDP7
	PAPLN	ENST00000555123.5	TSL:1	n.435G>T		non_coding_transcript_exon	Exon 6 of 24	ENSP00000452455.1	G3V5P6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.081	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.43
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.12
Sift	Benign	0.061	T
Sift4G	Benign	0.065	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.62
Mutation Taster		=88/12	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-73716792;