20-23421401-A-C
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_022080.3(NAPB):c.2T>G(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.0000122 in 1,391,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
NAPB
NM_022080.3 start_lost
NM_022080.3 start_lost
Scores
5
7
3
Clinical Significance
Conservation
PhyloP100: 5.91
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 Pathogenic. Variant got 10 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NAPB | NM_022080.3 | c.2T>G | p.Met1? | start_lost | 1/11 | ENST00000377026.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NAPB | ENST00000377026.4 | c.2T>G | p.Met1? | start_lost | 1/11 | 1 | NM_022080.3 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome AF: 0.0000122 AC: 17AN: 1391464Hom.: 0 Cov.: 32 AF XY: 0.0000131 AC XY: 9AN XY: 686706
GnomAD4 exome
AF:
AC:
17
AN:
1391464
Hom.:
Cov.:
32
AF XY:
AC XY:
9
AN XY:
686706
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 NFE exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy-107 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Intergen, Intergen Genetics and Rare Diseases Diagnosis Center | Nov 21, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PROVEAN
Benign
N;.;N
REVEL
Uncertain
Sift
Pathogenic
D;.;D
Sift4G
Pathogenic
D;D;D
Polyphen
0.99
.;.;D
Vest4
MutPred
Gain of MoRF binding (P = 0.0196);Gain of MoRF binding (P = 0.0196);Gain of MoRF binding (P = 0.0196);
MVP
ClinPred
D
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