rs363006

chr20-10299435-G-A

Variant summary

Our verdict is Benign. Variant got -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:2
• Conservation: PhyloP100: 1.31

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP25	NM_130811.4	c.552+23G>A		intron_variant		ENST00000254976.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP25	ENST00000254976.7	c.552+23G>A		intron_variant		1	NM_130811.4	P5
SNAP25-AS1	ENST00000421143.6	n.5+69280C>T		intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes AF: 0.174 AC: 42984 AN: 246758 Hom.: 4300 AF XY: 0.165 AC XY: 22057 AN XY: 133392

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 SAS exome AF: 0.0975

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

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.314

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.0902

Gnomad4 SAS exome AF: 0.0971

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.165

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

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.0865

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.177

Alfa AF: 0.173 Hom.: 2614

Bravo AF: 0.173

Asia WGS AF: 0.111 AC: 385 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 08, 2021

- -

Congenital myasthenic syndrome 18 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	7.7
Dann	Benign	0.87

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: rs363006; hg19: chr20-10280083;