20-23421338-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_022080.3(NAPB):c.65A>G(p.Lys22Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,565,400 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 4 hom., cov: 34)

Exomes 𝑓: 0.0017 ( 52 hom. )

Consequence

NAPB
NM_022080.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.89

Variant links:

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]

NAPB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030188859).

BP6

Variant 20-23421338-T-C is Benign according to our data. Variant chr20-23421338-T-C is described in ClinVar as [Benign]. Clinvar id is 709378.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.002 (304/152262) while in subpopulation EAS AF= 0.0463 (239/5160). AF 95% confidence interval is 0.0415. There are 4 homozygotes in gnomad4. There are 165 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAPB	NM_022080.3 link	c.65A>G	p.Lys22Arg	missense_variant	Exon 1 of 11	ENST00000377026.4	NP_071363.1	Q9H115-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAPB	ENST00000377026.4 link	c.65A>G	p.Lys22Arg	missense_variant	Exon 1 of 11	1	NM_022080.3	ENSP00000366225.4		Q9H115-1

Frequencies

GnomAD3 genomes

AF:

0.00200

AC:

305

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0464

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00439

AC:

769

AN:

175204

Hom.:

AF XY:

0.00409

AC XY:

385

AN XY:

94018

show subpopulations

Gnomad AFR exome

AF:

0.0000971

Gnomad AMR exome

AF:

0.00461

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0451

Gnomad SAS exome

AF:

0.000787

Gnomad FIN exome

AF:

0.000796

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.00152

GnomAD4 exome

AF:

0.00167

AC:

2360

AN:

1413138

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

1082

AN XY:

699042

show subpopulations

Gnomad4 AFR exome

AF:

0.0000627

Gnomad4 AMR exome

AF:

0.00412

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0500

Gnomad4 SAS exome

AF:

0.000671

Gnomad4 FIN exome

AF:

0.000465

Gnomad4 NFE exome

AF:

0.000184

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.00200

AC:

304

AN:

152262

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

165

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0463

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00220

Hom.:

Bravo

AF:

0.00249

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000235

AC:

ExAC

AF:

0.00328

AC:

384

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NAPB-related disorder

Benign:1

Sep 30, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Dec 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

.;.;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.071

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.85

D;D;D

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.9

L;.;L

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.1

N;.;N

REVEL

Uncertain

0.30

Sift

Benign

0.11

T;.;T

Sift4G

Benign

0.083

T;T;T

Polyphen

0.010

.;.;B

Vest4

0.25

MVP

0.69

MPC

0.68

ClinPred

0.012

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.36

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over