20-23395141-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_022080.3(NAPB):c.340A>G(p.Met114Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000031 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
NAPB
NM_022080.3 missense, splice_region
NM_022080.3 missense, splice_region
Scores
7
8
2
Splicing: ADA: 0.1946
2
Clinical Significance
Conservation
PhyloP100: 5.14
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 2 ACMG points.
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.340A>G | p.Met114Val | missense_variant, splice_region_variant | 4/11 | ENST00000377026.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NAPB | ENST00000377026.4 | c.340A>G | p.Met114Val | missense_variant, splice_region_variant | 4/11 | 1 | NM_022080.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000722 AC: 11AN: 152252Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250996Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135636
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 727224
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GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74382
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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 09, 2023 | The c.340A>G (p.M114V) alteration is located in exon 4 (coding exon 4) of the NAPB gene. This alteration results from a A to G substitution at nucleotide position 340, causing the methionine (M) at amino acid position 114 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
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;.;D
REVEL
Pathogenic
Sift
Uncertain
D;.;D
Sift4G
Benign
T;D;D
Polyphen
0.88
.;.;P
Vest4
MVP
MPC
0.58
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at