rs363050

Variant names:

• chr20-10253609-G-A
• rs363050
• NM_130811.4:c.-63-21820G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_130811.4(SNAP25):​c.-63-21820G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,910 control chromosomes in the GnomAD database, including 24,456 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.56 (24456 hom., cov: 31)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.230
• Publications: 43 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-10253609-G-A is Benign according to our data. Variant chr20-10253609-G-A is described in ClinVar as Benign. ClinVar VariationId is 542731.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.-63-21820G>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.-63-21820G>A		intron_variant	Intron 1 of 7	1	NM_130811.4	ENSP00000254976.3

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85316 AN: 151792 Hom.: 24435 Cov.: 31

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.562 AC: 85390 AN: 151910 Hom.: 24456 Cov.: 31 AF XY: 0.553 AC XY: 41053 AN XY: 74212

African (AFR) AF: 0.618 AC: 25638 AN: 41466

American (AMR) AF: 0.513 AC: 7840 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2145 AN: 3464

East Asian (EAS) AF: 0.293 AC: 1510 AN: 5154

South Asian (SAS) AF: 0.495 AC: 2372 AN: 4794

European-Finnish (FIN) AF: 0.461 AC: 4845 AN: 10520

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39184 AN: 67926

Other (OTH) AF: 0.557 AC: 1177 AN: 2114

Alfa AF: 0.556 Hom.: 14441

Bravo AF: 0.566

Asia WGS AF: 0.415 AC: 1444 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital myasthenic syndrome 18 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.32
PhyloP100		0.23
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: rs363050; hg19: chr20-10234257;