rs495484

Positions:

• chr18-10535063-T-A

Variant summary

Our verdict is Benign. Variant got -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

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]

NAPG (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NAPG	NM_003826.3	c.258+567T>A		intron_variant		ENST00000322897.11	NP_003817.1
NAPG	XM_011525754.3	c.438+567T>A		intron_variant			XP_011524056.1
NAPG	XM_011525756.3	c.12+567T>A		intron_variant			XP_011524058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAPG	ENST00000322897.11	c.258+567T>A		intron_variant		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

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.342

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs495484; hg19: chr18-10535060;