chr18-10540712-C-G

Position:

• chr18-10540712-C-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+313C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 217,832 control chromosomes in the GnomAD database, including 1,965 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 0.087 (1821 hom., cov: 33)
  • Exomes 𝑓: 0.020 (144 hom.)
• Consequence: NAPG NM_003826.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAPG	NM_003826.3	c.506+313C>G		intron_variant		ENST00000322897.11
NAPG	XM_011525754.3	c.686+313C>G		intron_variant
NAPG	XM_011525756.3	c.260+313C>G		intron_variant
NAPG	XM_017026063.3	c.251+313C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAPG	ENST00000322897.11	c.506+313C>G		intron_variant		1	NM_003826.3	P1

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 13189 AN: 152006 Hom.: 1811 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.0617

GnomAD4 exome AF: 0.0201 AC: 1318 AN: 65708 Hom.: 144 Cov.: 0 AF XY: 0.0186 AC XY: 624 AN XY: 33472

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.0266

Gnomad4 ASJ exome AF: 0.0374

Gnomad4 EAS exome AF: 0.0220

Gnomad4 SAS exome AF: 0.0124

Gnomad4 FIN exome AF: 0.000603

Gnomad4 NFE exome AF: 0.00205

Gnomad4 OTH exome AF: 0.0337

GnomAD4 genome AF: 0.0869 AC: 13227 AN: 152124 Hom.: 1821 Cov.: 33 AF XY: 0.0847 AC XY: 6299 AN XY: 74390

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.0327

Gnomad4 ASJ AF: 0.0398

Gnomad4 EAS AF: 0.0226

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00210

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.0578 Hom.: 129

Bravo AF: 0.100

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.2
DANN	Benign	0.58

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: rs9962325; hg19: chr18-10540709;