rs775186460

Variant names:

• chr14-73250077-C-G
• NM_001365906.3:c.428C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-73250077-C-G
• chr14-73250077-C-T

Variant summary

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

The NM_001365906.3(PAPLN):​c.428C>G​(p.Pro143Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,132 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PAPLN NM_001365906.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.01

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPLN	NM_001365906.3	c.428C>G	p.Pro143Arg	missense_variant	Exon 6 of 27	ENST00000644200.2	NP_001352835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPLN	ENST00000644200.2	c.428C>G	p.Pro143Arg	missense_variant	Exon 6 of 27		NM_001365906.3	ENSP00000495882.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460132 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T;.;T;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	D;D;.;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.68	D;D;D;D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.5	M;M;M;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.6	.;D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.018	.;D;D;D
Sift4G	Uncertain	0.015	.;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.71, 0.58, 0.58
MutPred		0.36		Loss of catalytic residue at P143 (P = 0.0736);Loss of catalytic residue at P143 (P = 0.0736);Loss of catalytic residue at P143 (P = 0.0736);Loss of catalytic residue at P143 (P = 0.0736);
MVP		0.61
MPC		0.76
ClinPred		0.98	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.51
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-73716785;