rs363006

Variant names:

• chr20-10299435-G-A
• rs363006
• NM_130811.4:c.552+23G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130811.4(SNAP25):​c.552+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,605,858 control chromosomes in the GnomAD database, including 22,349 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2141 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20208 hom.)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.31
• Publications: 21 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 20-10299435-G-A is Benign according to our data. Variant chr20-10299435-G-A is described in ClinVar as Benign. ClinVar VariationId is 1239527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130811.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	NM_130811.4	MANE Select	c.552+23G>A		intron	N/A	NP_570824.1	P60880-1
	SNAP25	NM_001322902.2		c.552+23G>A		intron	N/A	NP_001309831.1	P60880-2
	SNAP25	NM_001322903.2		c.552+23G>A		intron	N/A	NP_001309832.1	P60880-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	ENST00000254976.7	TSL:1 MANE Select	c.552+23G>A		intron	N/A	ENSP00000254976.3	P60880-1
	SNAP25	ENST00000304886.6	TSL:1	c.552+23G>A		intron	N/A	ENSP00000307341.2	P60880-2
	SNAP25	ENST00000961779.1		c.636+23G>A		intron	N/A	ENSP00000631838.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24577 AN: 151996 Hom.: 2137 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0866

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.177

GnomAD2 exomes AF: 0.174 AC: 42984 AN: 246758 AF XY: 0.165

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.323

Gnomad ASJ exome AF: 0.237

Gnomad EAS exome AF: 0.110

Gnomad FIN exome AF: 0.152

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.161 AC: 234697 AN: 1453744 Hom.: 20208 Cov.: 31 AF XY: 0.159 AC XY: 114810 AN XY: 722168

African (AFR) AF: 0.135 AC: 4485 AN: 33268

American (AMR) AF: 0.314 AC: 13876 AN: 44258

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 6282 AN: 25968

East Asian (EAS) AF: 0.0902 AC: 3551 AN: 39388

South Asian (SAS) AF: 0.0971 AC: 8329 AN: 85784

European-Finnish (FIN) AF: 0.150 AC: 7961 AN: 52980

Middle Eastern (MID) AF: 0.164 AC: 932 AN: 5674

European-Non Finnish (NFE) AF: 0.162 AC: 179409 AN: 1106414

Other (OTH) AF: 0.165 AC: 9872 AN: 60010

GnomAD4 genome AF: 0.162 AC: 24603 AN: 152114 Hom.: 2141 Cov.: 32 AF XY: 0.162 AC XY: 12075 AN XY: 74370

African (AFR) AF: 0.134 AC: 5553 AN: 41510

American (AMR) AF: 0.262 AC: 3995 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 850 AN: 3468

East Asian (EAS) AF: 0.106 AC: 549 AN: 5178

South Asian (SAS) AF: 0.0865 AC: 416 AN: 4812

European-Finnish (FIN) AF: 0.152 AC: 1605 AN: 10576

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.163 AC: 11103 AN: 67982

Other (OTH) AF: 0.177 AC: 374 AN: 2114

Alfa AF: 0.174 Hom.: 3426

Bravo AF: 0.173

Asia WGS AF: 0.111 AC: 385 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital myasthenic syndrome 18 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.7
DANN	Benign	0.87
PhyloP100		1.3
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: rs363006; hg19: chr20-10280083;