rs9302112

Positions:

• chr15-42528253-C-T

Variant summary

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

The NM_003825.4(SNAP23):​c.267-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,612,062 control chromosomes in the GnomAD database, including 421,573 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 0.57 (29945 hom., cov: 30)
  • Exomes 𝑓: 0.73 (391628 hom.)
• Consequence: SNAP23 NM_003825.4 intron
• Scores: Splicing: ADA: 0.00001875
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

Genes affected

SNAP23 (HGNC:11131): (synaptosome associated protein 23) Specificity of vesicular transport is regulated, in part, by the interaction of a vesicle-associated membrane protein termed synaptobrevin/VAMP with a target compartment membrane protein termed syntaxin. These proteins, together with SNAP25 (synaptosome-associated protein of 25 kDa), form a complex which serves as a binding site for the general membrane fusion machinery. Synaptobrevin/VAMP and syntaxin are believed to be involved in vesicular transport in most, if not all cells, while SNAP25 is present almost exclusively in the brain, suggesting that a ubiquitously expressed homolog of SNAP25 exists to facilitate transport vesicle/target membrane fusion in other tissues. The protein encoded by this gene is structurally and functionally similar to SNAP25 and binds tightly to multiple syntaxins and synaptobrevins/VAMPs. It is an essential component of the high affinity receptor for the general membrane fusion machinery and is an important regulator of transport vesicle docking and fusion. Two alternative transcript variants encoding different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ENSG00000285942 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAP23	NM_003825.4	c.267-9C>T		intron_variant		ENST00000249647.8	NP_003816.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAP23	ENST00000249647.8	c.267-9C>T		intron_variant		1	NM_003825.4	ENSP00000249647.3
ENSG00000285942	ENST00000650210.1	n.*240+74G>A		intron_variant				ENSP00000497618.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86743 AN: 151792 Hom.: 29943 Cov.: 30

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.583

GnomAD3 exomes AF: 0.678 AC: 170215 AN: 250918 Hom.: 60724 AF XY: 0.689 AC XY: 93536 AN XY: 135752

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.569

Gnomad ASJ exome AF: 0.665

Gnomad EAS exome AF: 0.784

Gnomad SAS exome AF: 0.646

Gnomad FIN exome AF: 0.809

Gnomad NFE exome AF: 0.753

Gnomad OTH exome AF: 0.685

GnomAD4 exome AF: 0.725 AC: 1058624 AN: 1460150 Hom.: 391628 Cov.: 35 AF XY: 0.724 AC XY: 526331 AN XY: 726490

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.562

Gnomad4 ASJ exome AF: 0.664

Gnomad4 EAS exome AF: 0.773

Gnomad4 SAS exome AF: 0.647

Gnomad4 FIN exome AF: 0.803

Gnomad4 NFE exome AF: 0.753

Gnomad4 OTH exome AF: 0.688

GnomAD4 genome AF: 0.571 AC: 86747 AN: 151912 Hom.: 29945 Cov.: 30 AF XY: 0.576 AC XY: 42752 AN XY: 74240

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.786

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.588

Alfa AF: 0.672 Hom.: 23614

Bravo AF: 0.538

Asia WGS AF: 0.662 AC: 2301 AN: 3478

EpiCase AF: 0.737

EpiControl AF: 0.733

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.6
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000019
dbscSNV1_RF	Benign	0.0
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: rs9302112; hg19: chr15-42820451;