rs1051312

chr20-10306440-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.99

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 -14 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_single_submitter, 1 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	UniProt
SNAP25	NM_130811.4	c.*243T>C		3_prime_UTR_variant	8/8	ENST00000254976.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP25	ENST00000254976.7	c.*243T>C		3_prime_UTR_variant	8/8	1	NM_130811.4	P5
SNAP25-AS1	ENST00000421143.6	n.5+62275A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29735 AN: 151750 Hom.: 3396 Cov.: 31

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.: 2 AF XY: 0.220 AC XY: 25897 AN XY: 117640

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.: 31 AF XY: 0.196 AC XY: 14509 AN XY: 74194

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	12
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

Other links and lift over

dbSNP: rs1051312; hg19: chr20-10287088;