rs9302112

Variant names:

• chr15-42528253-C-T
• rs9302112
• NM_003825.4:c.267-9C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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:):

LRRC57 (HGNC:26719): (leucine rich repeat containing 57) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SNAP23	NM_003825.4	c.267-9C>T		intron_variant	Intron 5 of 7	ENST00000249647.8	NP_003816.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP23	ENST00000249647.8	c.267-9C>T		intron_variant	Intron 5 of 7	1	NM_003825.4	ENSP00000249647.3
ENSG00000285942	ENST00000650210.1	n.*240+74G>A		intron_variant	Intron 7 of 8			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

GnomAD2 exomes AF: 0.678 AC: 170215 AN: 250918 AF XY: 0.689

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 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

African (AFR) AF: 0.143 AC: 4798 AN: 33466

American (AMR) AF: 0.562 AC: 25108 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 17328 AN: 26116

East Asian (EAS) AF: 0.773 AC: 30668 AN: 39682

South Asian (SAS) AF: 0.647 AC: 55762 AN: 86196

European-Finnish (FIN) AF: 0.803 AC: 42871 AN: 53378

Middle Eastern (MID) AF: 0.672 AC: 3871 AN: 5758

European-Non Finnish (NFE) AF: 0.753 AC: 836693 AN: 1110514

Other (OTH) AF: 0.688 AC: 41525 AN: 60342

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

African (AFR) AF: 0.162 AC: 6710 AN: 41394

American (AMR) AF: 0.577 AC: 8809 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2267 AN: 3464

East Asian (EAS) AF: 0.786 AC: 4055 AN: 5158

South Asian (SAS) AF: 0.633 AC: 3038 AN: 4802

European-Finnish (FIN) AF: 0.795 AC: 8387 AN: 10550

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.755 AC: 51351 AN: 67970

Other (OTH) AF: 0.588 AC: 1239 AN: 2108

Alfa AF: 0.672 Hom.: 25660

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
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9302112; hg19: chr15-42820451;