rs1566673792

Variant names:

• chr14-73246088-G-A
• rs1566673792
• NM_001365906.3:c.247G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-73246088-G-A
• chr14-73246088-G-C
• chr14-73246088-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365906.3(PAPLN):​c.247G>A​(p.Ala83Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,415,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PAPLN NM_001365906.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1247901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPLN	NM_001365906.3	c.247G>A	p.Ala83Thr	missense_variant	Exon 5 of 27	ENST00000644200.2	NP_001352835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPLN	ENST00000644200.2	c.247G>A	p.Ala83Thr	missense_variant	Exon 5 of 27		NM_001365906.3	ENSP00000495882.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000572 AC: 1 AN: 174730 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 96868

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000857

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1415410 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 701884

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000568

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.0067	T;.;T;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T;T;.;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.78	N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	.;N;N;N
REVEL	Benign	0.065
Sift	Benign	0.55	.;T;T;T
Sift4G	Benign	0.30	.;T;T;T
Polyphen		0.040	B;B;B;B
Vest4		0.24, 0.28, 0.28
MutPred		0.25		Gain of glycosylation at A83 (P = 0.0146);Gain of glycosylation at A83 (P = 0.0146);Gain of glycosylation at A83 (P = 0.0146);Gain of glycosylation at A83 (P = 0.0146);
MVP		0.040
MPC		0.19
ClinPred		0.10	T
GERP RS		1.9
Varity_R		0.037
gMVP		0.33

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: rs1566673792; hg19: chr14-73712796;