ENST00000398425.7:c.1_2delATinsTA

Variant names:

• chr20-23397130-AT-TA
• ENST00000398425.7:c.1_2delATinsTA
• NAPB p.Met1?

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The ENST00000398425.7(NAPB):​c.1_2delATinsTA​(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NAPB ENST00000398425.7 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.01
• Publications: 0 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: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Start lost variant, no new inframe start found.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000398425.7. 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.236_237delATinsTA	p.His79Leu	missense	N/A	NP_071363.1	Q9H115-1
	NAPB	NM_001283026.2		c.1_2delATinsTA	p.Met1?	start_lost	N/A	NP_001269955.1	Q9H115-3
	NAPB	NM_001283018.2		c.248_249delATinsTA	p.His83Leu	missense	N/A	NP_001269947.1	A0A087WZQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAPB	ENST00000398425.7	TSL:1	c.1_2delATinsTA	p.Met1?	start_lost	N/A	ENSP00000381459.3	Q9H115-3
	NAPB	ENST00000377026.4	TSL:1 MANE Select	c.236_237delATinsTA	p.His79Leu	missense	N/A	ENSP00000366225.4	Q9H115-1
	NAPB	ENST00000617876.4	TSL:2	c.248_249delATinsTA	p.His83Leu	missense	N/A	ENSP00000482826.1	A0A087WZQ7

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-23377767;