rs362562

Variant names:

• chr20-10262538-G-A
• rs362562
• NM_130811.4:c.-63-12891G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130811.4(SNAP25):​c.-63-12891G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,862 control chromosomes in the GnomAD database, including 10,738 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 0.36 (10738 hom., cov: 32)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138

Genes affected

SNAP25 (HGNC:11132): (synaptosome associated protein 25) Synaptic vesicle membrane docking and fusion is mediated by SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) located on the vesicle membrane (v-SNAREs) and the target membrane (t-SNAREs). The assembled v-SNARE/t-SNARE complex consists of a bundle of four helices, one of which is supplied by v-SNARE and the other three by t-SNARE. For t-SNAREs on the plasma membrane, the protein syntaxin supplies one helix and the protein encoded by this gene contributes the other two. Therefore, this gene product is a presynaptic plasma membrane protein involved in the regulation of neurotransmitter release. Two alternative transcript variants encoding different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

SNAP25-AS1 (HGNC:44312): (SNAP25 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.-63-12891G>A		intron_variant	Intron 1 of 7	ENST00000254976.7	NP_570824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7	c.-63-12891G>A		intron_variant	Intron 1 of 7	1	NM_130811.4	ENSP00000254976.3

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54938 AN: 151748 Hom.: 10740 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.0904

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.362 AC: 54961 AN: 151862 Hom.: 10738 Cov.: 32 AF XY: 0.359 AC XY: 26662 AN XY: 74204

Gnomad4 AFR AF: 0.253 AC: 0.253438 AN: 0.253438

Gnomad4 AMR AF: 0.404 AC: 0.404364 AN: 0.404364

Gnomad4 ASJ AF: 0.546 AC: 0.546398 AN: 0.546398

Gnomad4 EAS AF: 0.0906 AC: 0.090608 AN: 0.090608

Gnomad4 SAS AF: 0.287 AC: 0.286547 AN: 0.286547

Gnomad4 FIN AF: 0.374 AC: 0.374288 AN: 0.374288

Gnomad4 NFE AF: 0.431 AC: 0.431071 AN: 0.431071

Gnomad4 OTH AF: 0.402 AC: 0.402277 AN: 0.402277

Alfa AF: 0.416 Hom.: 22732

Bravo AF: 0.359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.75
Mutation Taster		=100/0	polymorphism (auto)

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: rs362562; hg19: chr20-10243186;