rs617040

Positions:

• chr18-10549365-C-A
• chr18-10549365-C-T

Variant summary

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

The ENST00000322897.11(NAPG):​c.795+269C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 152,038 control chromosomes in the GnomAD database, including 27,157 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 0.58 (27157 hom., cov: 32)
• Consequence: NAPG ENST00000322897.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAPG	NM_003826.3	c.795+269C>A		intron_variant		ENST00000322897.11	NP_003817.1
NAPG	XM_011525754.3	c.975+269C>A		intron_variant			XP_011524056.1
NAPG	XM_011525756.3	c.549+269C>A		intron_variant			XP_011524058.1
NAPG	XM_017026063.3	c.540+269C>A		intron_variant			XP_016881552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAPG	ENST00000322897.11	c.795+269C>A		intron_variant		1	NM_003826.3	ENSP00000324628	P1
NAPG	ENST00000580224.5	c.*658+269C>A		intron_variant, NMD_transcript_variant		2		ENSP00000463265
NAPG	ENST00000580483.5	c.*536+269C>A		intron_variant, NMD_transcript_variant		3		ENSP00000464496
NAPG	ENST00000583367.1	n.1175+269C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87478 AN: 151920 Hom.: 27117 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.576 AC: 87569 AN: 152038 Hom.: 27157 Cov.: 32 AF XY: 0.570 AC XY: 42371 AN XY: 74282

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.537

Alfa AF: 0.564 Hom.: 3721

Bravo AF: 0.594

Asia WGS AF: 0.532 AC: 1849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.056
DANN	Benign	0.36

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: rs617040; hg19: chr18-10549362;