15-73633202-G-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_012428.4(NPTN):c.14C>A(p.Ser5Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NPTN
NM_012428.4 stop_gained
NM_012428.4 stop_gained
Scores
2
1
4
Clinical Significance
Conservation
PhyloP100: 0.585
Genes affected
NPTN (HGNC:17867): (neuroplastin) This gene encodes a type I transmembrane protein belonging to the Ig superfamily. The protein is believed to be involved in cell-cell interactions or cell-substrate interactions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.988 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPTN | NM_012428.4 | c.14C>A | p.Ser5Ter | stop_gained | 1/9 | ENST00000345330.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPTN | ENST00000345330.9 | c.14C>A | p.Ser5Ter | stop_gained | 1/9 | 1 | NM_012428.4 | P4 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1376786Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 684032
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1376786
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
684032
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine | Apr 09, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Benign
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
MutationTaster
Benign
A;A;A;A;A;A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.