20-23374786-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022080.3(NAPB):c.*2590G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,696 control chromosomes in the GnomAD database, including 4,894 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4879 hom., cov: 32)
  • Exomes 𝑓: 0.41 (15 hom.)
• Consequence: NAPB NM_022080.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAPB	NM_022080.3	c.*2590G>A		3_prime_UTR_variant	11/11	ENST00000377026.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAPB	ENST00000377026.4	c.*2590G>A		3_prime_UTR_variant	11/11	1	NM_022080.3	P3
NAPB	ENST00000398425.7	c.*2590G>A		3_prime_UTR_variant	10/10	1
NAPB	ENST00000432543.6	c.*2590G>A		3_prime_UTR_variant	10/10	2
NAPB	ENST00000617876.4	c.*2590G>A		3_prime_UTR_variant	11/11	2		A1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34359 AN: 151390 Hom.: 4879 Cov.: 32

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.0510

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.405 AC: 77 AN: 190 Hom.: 15 Cov.: 0 AF XY: 0.395 AC XY: 45 AN XY: 114

Gnomad4 FIN exome AF: 0.410

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.227 AC: 34359 AN: 151506 Hom.: 4879 Cov.: 32 AF XY: 0.230 AC XY: 16990 AN XY: 74008

Gnomad4 AFR AF: 0.0723

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.0503

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.214

Alfa AF: 0.266 Hom.: 7764

Bravo AF: 0.196

Asia WGS AF: 0.232 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	8.8
Dann	Benign	0.77

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

Other links and lift over

dbSNP: rs8615; hg19: chr20-23355423;