rs510110

chr18-10540435-A-Cchr18-10540435-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003826.3(NAPG):c.506+36A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,558,412 control chromosomes in the GnomAD database, including 93,854 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 0.34 (9049 hom., cov: 33)
  • Exomes 𝑓: 0.35 (84805 hom.)
• Consequence: NAPG NM_003826.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAPG	NM_003826.3	c.506+36A>C		intron_variant		ENST00000322897.11
NAPG	XM_011525754.3	c.686+36A>C		intron_variant
NAPG	XM_011525756.3	c.260+36A>C		intron_variant
NAPG	XM_017026063.3	c.251+36A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAPG	ENST00000322897.11	c.506+36A>C		intron_variant		1	NM_003826.3	P1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52270 AN: 151998 Hom.: 9044 Cov.: 33

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.352

GnomAD3 exomes AF: 0.341 AC: 80687 AN: 236844 Hom.: 14045 AF XY: 0.340 AC XY: 43715 AN XY: 128598

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.294

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.425

Gnomad SAS exome AF: 0.293

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.353

Gnomad OTH exome AF: 0.349

GnomAD4 exome AF: 0.346 AC: 486069 AN: 1406296 Hom.: 84805 Cov.: 22 AF XY: 0.344 AC XY: 241518 AN XY: 701846

Gnomad4 AFR exome AF: 0.345

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.449

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.349

Gnomad4 OTH exome AF: 0.339

GnomAD4 genome AF: 0.344 AC: 52287 AN: 152116 Hom.: 9049 Cov.: 33 AF XY: 0.342 AC XY: 25403 AN XY: 74336

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.349

Alfa AF: 0.284 Hom.: 1396

Bravo AF: 0.344

Asia WGS AF: 0.311 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.38
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs510110; hg19: chr18-10540432; COSMIC: COSV59796628; COSMIC: COSV59796628;