18-10535063-T-A

Variant names:

• chr18-10535063-T-A
• rs495484
• NM_003826.3:c.258+567T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003826.3(NAPG):​c.258+567T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,152 control chromosomes in the GnomAD database, including 8,621 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 0.33 (8621 hom., cov: 33)
• Consequence: NAPG NM_003826.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 2 publications found

Genes affected

NAPG (HGNC:7642): (NSF attachment protein gamma) This gene encodes soluble NSF attachment protein gamma. The soluble NSF attachment proteins (SNAPs) enable N-ethyl-maleimide-sensitive fusion protein (NSF) to bind to target membranes. NSF and SNAPs appear to be general components of the intracellular membrane fusion apparatus, and their action at specific sites of fusion must be controlled by SNAP receptors particular to the membranes being fused. The product of this gene mediates platelet exocytosis and controls the membrane fusion events of this process.[provided by RefSeq, Dec 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAPG	NM_003826.3	c.258+567T>A		intron_variant	Intron 5 of 11	ENST00000322897.11	NP_003817.1
NAPG	XM_011525754.3	c.438+567T>A		intron_variant	Intron 6 of 12		XP_011524056.1
NAPG	XM_011525756.3	c.12+567T>A		intron_variant	Intron 3 of 9		XP_011524058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAPG	ENST00000322897.11	c.258+567T>A		intron_variant	Intron 5 of 11	1	NM_003826.3	ENSP00000324628.6

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50877 AN: 152034 Hom.: 8617 Cov.: 33

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.334 AC: 50894 AN: 152152 Hom.: 8621 Cov.: 33 AF XY: 0.333 AC XY: 24792 AN XY: 74370

African (AFR) AF: 0.310 AC: 12890 AN: 41516

American (AMR) AF: 0.318 AC: 4862 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1138 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2208 AN: 5178

South Asian (SAS) AF: 0.294 AC: 1418 AN: 4824

European-Finnish (FIN) AF: 0.323 AC: 3414 AN: 10576

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23764 AN: 67996

Other (OTH) AF: 0.342 AC: 723 AN: 2114

Alfa AF: 0.345 Hom.: 1138

Bravo AF: 0.333

Asia WGS AF: 0.317 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.58
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs495484; hg19: chr18-10535060;