rs362563

Variant names:

• chr20-10262603-T-C
• rs362563
• NM_130811.4:c.-63-12826T>C

Variant summary

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

The NM_130811.4(SNAP25):​c.-63-12826T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,012 control chromosomes in the GnomAD database, including 1,095 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 0.10 (1095 hom., cov: 31)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• Publications: 3 publications found

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.-63-12826T>C		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.-63-12826T>C		intron_variant	Intron 1 of 7	1	NM_130811.4	ENSP00000254976.3

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15253 AN: 151896 Hom.: 1090 Cov.: 31

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0908

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0979

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0488

Gnomad OTH AF: 0.0868

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

GnomAD4 genome AF: 0.101 AC: 15283 AN: 152012 Hom.: 1095 Cov.: 31 AF XY: 0.103 AC XY: 7632 AN XY: 74264

African (AFR) AF: 0.172 AC: 7117 AN: 41438

American (AMR) AF: 0.0916 AC: 1398 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0427 AC: 148 AN: 3470

East Asian (EAS) AF: 0.276 AC: 1429 AN: 5174

South Asian (SAS) AF: 0.118 AC: 565 AN: 4802

European-Finnish (FIN) AF: 0.0979 AC: 1033 AN: 10550

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.0489 AC: 3322 AN: 68000

Other (OTH) AF: 0.0859 AC: 181 AN: 2108

Alfa AF: 0.0730 Hom.: 1156

Bravo AF: 0.106

Asia WGS AF: 0.164 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.63
PhyloP100		-0.47
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

Other links and lift over

dbSNP: rs362563; hg19: chr20-10243251;