rs1051312

Variant names:

• chr20-10306440-T-C
• rs1051312
• NM_130811.4:c.*243T>C

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.*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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.99
• Publications: 55 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=-0.6).
• BP6: Variant 20-10306440-T-C is Benign according to our data. Variant chr20-10306440-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	NM_130811.4	MANE Select	c.*243T>C		3_prime_UTR	Exon 8 of 8	NP_570824.1
	SNAP25	NM_001322902.2		c.*243T>C		3_prime_UTR	Exon 8 of 8	NP_001309831.1
	SNAP25	NM_001322903.2		c.*243T>C		3_prime_UTR	Exon 9 of 9	NP_001309832.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	ENST00000254976.7	TSL:1 MANE Select	c.*243T>C		3_prime_UTR	Exon 8 of 8	ENSP00000254976.3
	SNAP25	ENST00000304886.6	TSL:1	c.*243T>C		3_prime_UTR	Exon 8 of 8	ENSP00000307341.2
	SNAP25	ENST00000495883.1	TSL:2	n.1278T>C		non_coding_transcript_exon	Exon 3 of 3

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

African (AFR) AF: 0.0951 AC: 620 AN: 6522

American (AMR) AF: 0.210 AC: 1582 AN: 7542

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 2344 AN: 8174

East Asian (EAS) AF: 0.000359 AC: 7 AN: 19522

South Asian (SAS) AF: 0.133 AC: 1065 AN: 8036

European-Finnish (FIN) AF: 0.307 AC: 6082 AN: 19798

Middle Eastern (MID) AF: 0.263 AC: 305 AN: 1158

European-Non Finnish (NFE) AF: 0.245 AC: 35140 AN: 143214

Other (OTH) AF: 0.213 AC: 3122 AN: 14648

GnomAD4 genome AF: 0.196 AC: 29756 AN: 151868 Hom.: 3393 Cov.: 31 AF XY: 0.196 AC XY: 14509 AN XY: 74194

African (AFR) AF: 0.0974 AC: 4040 AN: 41458

American (AMR) AF: 0.211 AC: 3216 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1018 AN: 3460

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5184

South Asian (SAS) AF: 0.154 AC: 737 AN: 4794

European-Finnish (FIN) AF: 0.306 AC: 3219 AN: 10526

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16828 AN: 67900

Other (OTH) AF: 0.192 AC: 404 AN: 2104

Alfa AF: 0.225 Hom.: 1479

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

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 15, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24391914)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		3.0
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: rs1051312; hg19: chr20-10287088;