14-73254537-GTC-CTG

Variant names:

• chr14-73254537-GTC-CTG
• NM_001365906.3:c.1327_1329delGTCinsCTG
• PAPLN p.Val443Leu

Variant summary

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

The NM_001365906.3(PAPLN):​c.1327_1329delGTCinsCTG​(p.Val443Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PAPLN NM_001365906.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• 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.

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.1327_1329delGTCinsCTG	p.Val443Leu	missense	N/A	NP_001352835.1	O95428-1
	PAPLN	NM_001365907.2		c.1327_1329delGTCinsCTG	p.Val443Leu	missense	N/A	NP_001352836.1	O95428-5
	PAPLN	NM_173462.4		c.1246_1248delGTCinsCTG	p.Val416Leu	missense	N/A	NP_775733.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPLN	ENST00000644200.2	MANE Select	c.1327_1329delGTCinsCTG	p.Val443Leu	missense	N/A	ENSP00000495882.2	O95428-1
	PAPLN	ENST00000216658.9	TSL:1	n.1327_1329delGTCinsCTG		non_coding_transcript_exon	Exon 13 of 27	ENSP00000216658.5	B5MDP7
	PAPLN	ENST00000555123.5	TSL:1	n.1246_1248delGTCinsCTG		non_coding_transcript_exon	Exon 12 of 24	ENSP00000452455.1	G3V5P6

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1

Splicing

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: chr14-73721245;