20-23394969-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_022080.3(NAPB):c.373A>G(p.Ile125Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
NAPB
NM_022080.3 missense
NM_022080.3 missense
Scores
1
2
14
Clinical Significance
Conservation
PhyloP100: 6.27
Genes affected
NAPB (HGNC:15751): (NSF attachment protein beta) This gene encodes a member of the soluble N-ethyl-maleimide-sensitive fusion attachment protein (SNAP) family. SNAP proteins play a critical role in the docking and fusion of vesicles to target membranes as part of the 20S NSF-SNAP-SNARE complex. This gene encodes the SNAP beta isoform which has been shown to be preferentially expressed in brain tissue. The encoded protein also interacts with the GluR2 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunit C-terminus and may play a role as a chaperone in the molecular processing of the AMPA receptor. [provided by RefSeq, Mar 2017]
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ACMG classification
Classification made for transcript
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=0.15388784).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NAPB | NM_022080.3 | c.373A>G | p.Ile125Val | missense_variant | 5/11 | ENST00000377026.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NAPB | ENST00000377026.4 | c.373A>G | p.Ile125Val | missense_variant | 5/11 | 1 | NM_022080.3 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2023 | The c.373A>G (p.I125V) alteration is located in exon 5 (coding exon 5) of the NAPB gene. This alteration results from a A to G substitution at nucleotide position 373, causing the isoleucine (I) at amino acid position 125 to be replaced by a valine (V). 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
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;N
REVEL
Benign
Sift
Benign
T;T;.;T
Sift4G
Benign
T;T;T;T
Polyphen
0.0010
.;.;.;B
Vest4
MutPred
0.36
.;.;.;Loss of catalytic residue at I125 (P = 0.0205);
MVP
MPC
0.54
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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.