NM_003827.4:c.618C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003827.4(NAPA):​c.618C>A​(p.Phe206Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

NAPA
NM_003827.4 missense

Scores

4
2
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67
Variant links:
Genes affected
NAPA (HGNC:7641): (NSF attachment protein alpha) This gene encodes a member of the soluble NSF 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. The encoded protein plays a role in the completion of membrane fusion by mediating the interaction of N-ethylmaleimide-sensitive factor (NSF) with the vesicle-associated and membrane-associated SNAP receptor (SNARE) complex, and stimulating the ATPase activity of NSF. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jun 2011]
NAPA-AS1 (HGNC:44118): (NAPA antisense RNA 1)

Genome browser will be placed here

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 rank MANE Protein UniProt
NAPANM_003827.4 linkc.618C>A p.Phe206Leu missense_variant Exon 8 of 11 ENST00000263354.8 NP_003818.2 P54920A0A024R0R9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NAPAENST00000263354.8 linkc.618C>A p.Phe206Leu missense_variant Exon 8 of 11 1 NM_003827.4 ENSP00000263354.2 P54920

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251418
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1461846
Hom.:
0
Cov.:
30
AF XY:
0.0000151
AC XY:
11
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000225
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152232
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 27, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.618C>A (p.F206L) alteration is located in exon 8 (coding exon 8) of the NAPA gene. This alteration results from a C to A substitution at nucleotide position 618, causing the phenylalanine (F) at amino acid position 206 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.92
BayesDel_addAF
Benign
-0.0096
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
25
DANN
Benign
0.95
DEOGEN2
Benign
0.32
T;T;.;.
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.0072
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Pathogenic
0.97
D;D;D;D
M_CAP
Benign
0.016
T
MetaRNN
Uncertain
0.57
D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;.;.;.
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-4.8
D;.;.;.
REVEL
Benign
0.21
Sift
Benign
0.80
T;.;.;.
Sift4G
Benign
0.67
T;T;.;.
Polyphen
0.15
B;.;.;.
Vest4
0.89
MutPred
0.73
Loss of ubiquitination at K208 (P = 0.1091);.;.;.;
MVP
0.71
MPC
0.32
ClinPred
0.45
T
GERP RS
4.0
Varity_R
0.50
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs775392241; hg19: chr19-47995320; API