14-73246148-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001365906.3(PAPLN):c.307C>T(p.Arg103Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000755 in 1,589,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000042 ( 0 hom. )
Consequence
PAPLN
NM_001365906.3 missense
NM_001365906.3 missense
Scores
8
11
Clinical Significance
Conservation
PhyloP100: 1.52
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40433452).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PAPLN | NM_001365906.3 | c.307C>T | p.Arg103Trp | missense_variant | 5/27 | ENST00000644200.2 | NP_001352835.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PAPLN | ENST00000644200.2 | c.307C>T | p.Arg103Trp | missense_variant | 5/27 | NM_001365906.3 | ENSP00000495882 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152176Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000417 AC: 6AN: 1437548Hom.: 0 Cov.: 31 AF XY: 0.00000420 AC XY: 3AN XY: 714918
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74338
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 06, 2022 | The c.307C>T (p.R103W) alteration is located in exon 5 (coding exon 4) of the PAPLN gene. This alteration results from a C to T substitution at nucleotide position 307, causing the arginine (R) at amino acid position 103 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
.;D;D;D
REVEL
Benign
Sift
Uncertain
.;D;D;D
Sift4G
Uncertain
.;D;D;D
Polyphen
D;D;D;D
Vest4
0.45, 0.47, 0.46
MutPred
Loss of disorder (P = 0.025);Loss of disorder (P = 0.025);Loss of disorder (P = 0.025);Loss of disorder (P = 0.025);
MVP
0.38
MPC
0.21
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at