Genetic Variant NM_003827.4:c.322A>G (chr19-47495570-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003827.4(NAPA):c.322A>G(p.Ile108Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000612 in 1,601,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

NAPA
NM_003827.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.01

Publications

0 publications found

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 links:

NAPA-AS1 (HGNC:44118): (NAPA antisense RNA 1)

NAPA-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2593234).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003827.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NAPA	NM_003827.4	MANE Select	c.322A>G	p.Ile108Val	missense	Exon 4 of 11	NP_003818.2
NAPA	NR_038456.2		n.445A>G		non_coding_transcript_exon	Exon 4 of 12
NAPA	NR_038457.2		n.248A>G		non_coding_transcript_exon	Exon 2 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAPA	ENST00000263354.8	TSL:1 MANE Select	c.322A>G	p.Ile108Val	missense	Exon 4 of 11	ENSP00000263354.2	P54920
NAPA	ENST00000595826.5	TSL:1	n.530A>G		non_coding_transcript_exon	Exon 5 of 7
NAPA	ENST00000602082.5	TSL:1	n.207A>G		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.0000349

AC:

AN:

143456

Hom.:

Cov.:

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:

0.0000769

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000439

AC:

AN:

250698

AF XY:

0.0000664

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000705

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000638

AC:

AN:

1457652

Hom.:

Cov.:

AF XY:

0.0000621

AC XY:

AN XY:

724752

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33396

American (AMR)

AF:

0.0000674

AC:

AN:

44498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39532

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000766

AC:

AN:

1109722

Other (OTH)

AF:

0.0000664

AC:

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000349

AC:

AN:

143456

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69676

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38546

American (AMR)

AF:

0.00

AC:

AN:

13988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3342

East Asian (EAS)

AF:

0.00

AC:

AN:

4926

South Asian (SAS)

AF:

0.00

AC:

AN:

4478

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10030

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0000769

AC:

AN:

65048

Other (OTH)

AF:

0.00

AC:

AN:

1944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000820

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.088

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.025

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.49

PhyloP100

8.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.32

REVEL

Benign

0.22

Sift

Benign

0.67

Sift4G

Benign

0.39

Polyphen

0.0010

Vest4

0.64

MutPred

0.60

Gain of MoRF binding (P = 0.2776)

MVP

0.60

MPC

0.23

ClinPred

0.14

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.035

gMVP

0.23

Mutation Taster

=76/24

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over