14-73251818-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001365906.3(PAPLN):c.825G>A(p.Ser275=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,596,868 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00083 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (1 hom.)
• Consequence: PAPLN NM_001365906.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.93

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

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 14-73251818-G-A is Benign according to our data. Variant chr14-73251818-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2644358.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.93 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAPLN	NM_001365906.3	c.825G>A	p.Ser275=	synonymous_variant	9/27	ENST00000644200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPLN	ENST00000644200.2	c.825G>A	p.Ser275=	synonymous_variant	9/27		NM_001365906.3	P1

Frequencies

GnomAD3 genomes AF: 0.000828 AC: 126 AN: 152096 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000858 AC: 195 AN: 227400 Hom.: 0 AF XY: 0.000903 AC XY: 113 AN XY: 125166

Gnomad AFR exome AF: 0.000211

Gnomad AMR exome AF: 0.000172

Gnomad ASJ exome AF: 0.000113

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000191

Gnomad NFE exome AF: 0.00174

Gnomad OTH exome AF: 0.000367

GnomAD4 exome AF: 0.00134 AC: 1933 AN: 1444654 Hom.: 1 Cov.: 33 AF XY: 0.00132 AC XY: 947 AN XY: 718628

Gnomad4 AFR exome AF: 0.000279

Gnomad4 AMR exome AF: 0.000204

Gnomad4 ASJ exome AF: 0.0000396

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000211

Gnomad4 NFE exome AF: 0.00168

Gnomad4 OTH exome AF: 0.000772

GnomAD4 genome AF: 0.000828 AC: 126 AN: 152214 Hom.: 0 Cov.: 33 AF XY: 0.000887 AC XY: 66 AN XY: 74396

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.000457

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00144

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000895 Hom.: 0

Bravo AF: 0.000790

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

PAPLN: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.11
Dann	Benign	0.90

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

Other links and lift over

dbSNP: rs375078700; hg19: chr14-73718526;