Variant rs1051312 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.*243T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 380,482 control chromosomes in the GnomAD database, including 9,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3393 hom., cov: 31)

Exomes 𝑓: 0.22 ( 6391 hom. )

Consequence

SNAP25
NM_130811.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.99

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:44312): (SNAP25 antisense RNA 1)

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=-0.6).

BP6

Variant 20-10306440-T-C is Benign according to our data. Variant chr20-10306440-T-C is described in ClinVar as [Benign]. Clinvar id is 1228823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAP25	NM_130811.4 link	c.*243T>C		3_prime_UTR_variant	8/8	ENST00000254976.7	NP_570824.1	P60880-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7 link	c.*243T>C		3_prime_UTR_variant	8/8	1	NM_130811.4	ENSP00000254976.3		P60880-1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29735

AN:

151750

Hom.:

3396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0972

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.294

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.191

GnomAD4 exome

AF:

0.220

AC:

50267

AN:

228614

Hom.:

6391

Cov.:

AF XY:

0.220

AC XY:

25897

AN XY:

117640

show subpopulations

Gnomad4 AFR exome

AF:

0.0951

Gnomad4 AMR exome

AF:

0.210

Gnomad4 ASJ exome

AF:

0.287

Gnomad4 EAS exome

AF:

0.000359

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.307

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.213

GnomAD4 genome

AF:

0.196

AC:

29756

AN:

151868

Hom.:

3393

Cov.:

AF XY:

0.196

AC XY:

14509

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.0974

Gnomad4 AMR

AF:

0.211

Gnomad4 ASJ

AF:

0.294

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.306

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.192

Alfa

AF:

0.220

Hom.:

856

Bravo

AF:

0.187

Asia WGS

AF:

0.0780

AC:

271

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Jul 15, 2020	This variant is associated with the following publications: (PMID: 24391914) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.81

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