Variant rs363006 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.31

Variant links:

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 links:

SNAP25-AS1 (HGNC:):

SNAP25-AS1 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
SNAP25	NM_130811.4 linkuse as main transcript	c.552+23G>A		intron_variant		ENST00000254976.7	NP_570824.1	P60880-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7 linkuse as main transcript	c.552+23G>A		intron_variant		1	NM_130811.4	ENSP00000254976.3		P60880-1

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24577

AN:

151996

Hom.:

2137

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.159

AC XY:

114810

AN XY:

722168

show subpopulations

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.:

AF XY:

0.162

AC XY:

12075

AN XY:

74370

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over