rs747462913

Variant names:

• chr20-23403046-C-A
• rs747462913
• ENST00000398425.7:c.-111G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-23403046-C-A
• chr20-23403046-C-G
• chr20-23403046-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001283026.2(NAPB):​c.-111G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAPB NM_001283026.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAPB	NM_022080.3	c.125G>T	p.Cys42Phe	missense_variant	Exon 2 of 11	ENST00000377026.4	NP_071363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAPB	ENST00000377026.4	c.125G>T	p.Cys42Phe	missense_variant	Exon 2 of 11	1	NM_022080.3	ENSP00000366225.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	.;.;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Uncertain	0.23	D
MutationAssessor	Uncertain	2.6	M;.;M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-4.3	D;.;D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.024	D;.;D
Sift4G	Benign	0.086	T;T;T
Polyphen		0.89	.;.;P
Vest4		0.88
MutPred		0.51		Gain of MoRF binding (P = 0.0774);Gain of MoRF binding (P = 0.0774);Gain of MoRF binding (P = 0.0774);
MVP		0.72
MPC		1.9
ClinPred		0.88	D
GERP RS		6.0
Varity_R		0.63
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs747462913; hg19: chr20-23383683;