20-23374786-C-T

Variant names:

• chr20-23374786-C-T
• rs8615
• NM_022080.3:c.*2590G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy 107

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022080.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAPB	NM_022080.3	MANE Select	c.*2590G>A		3_prime_UTR	Exon 11 of 11	NP_071363.1	Q9H115-1
	NAPB	NM_001283018.2		c.*2590G>A		3_prime_UTR	Exon 11 of 11	NP_001269947.1	A0A087WZQ7
	NAPB	NM_001283020.2		c.*2590G>A		3_prime_UTR	Exon 10 of 10	NP_001269949.1	Q9H115-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAPB	ENST00000377026.4	TSL:1 MANE Select	c.*2590G>A		3_prime_UTR	Exon 11 of 11	ENSP00000366225.4	Q9H115-1
	NAPB	ENST00000398425.7	TSL:1	c.*2590G>A		3_prime_UTR	Exon 10 of 10	ENSP00000381459.3	Q9H115-3
	NAPB	ENST00000617876.4	TSL:2	c.*2590G>A		3_prime_UTR	Exon 11 of 11	ENSP00000482826.1	A0A087WZQ7

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.410 AC: 77 AN: 188

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.0723 AC: 2984 AN: 41296

American (AMR) AF: 0.192 AC: 2917 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 915 AN: 3470

East Asian (EAS) AF: 0.0503 AC: 258 AN: 5126

South Asian (SAS) AF: 0.385 AC: 1848 AN: 4800

European-Finnish (FIN) AF: 0.407 AC: 4273 AN: 10486

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.301 AC: 20462 AN: 67870

Other (OTH) AF: 0.214 AC: 448 AN: 2094

Alfa AF: 0.248 Hom.: 11117

Bravo AF: 0.196

Asia WGS AF: 0.232 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.8
DANN	Benign	0.77
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8615; hg19: chr20-23355423;