NM_130811.4:c.330C>T

Variant names:

• chr20-10296973-C-T
• rs362998
• NM_130811.4:c.330C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_130811.4(SNAP25):​c.330C>T​(p.Asp110Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0818 in 1,613,744 control chromosomes in the GnomAD database, including 7,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1153 hom., cov: 33)
  • Exomes 𝑓: 0.079 (5974 hom.)
• Consequence: SNAP25 NM_130811.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.528
• Publications: 27 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 20-10296973-C-T is Benign according to our data. Variant chr20-10296973-C-T is described in ClinVar as Benign. ClinVar VariationId is 587804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.528 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	NM_130811.4	MANE Select	c.330C>T	p.Asp110Asp	synonymous	Exon 6 of 8	NP_570824.1
	SNAP25	NM_001322902.2		c.330C>T	p.Asp110Asp	synonymous	Exon 6 of 8	NP_001309831.1
	SNAP25	NM_001322903.2		c.330C>T	p.Asp110Asp	synonymous	Exon 7 of 9	NP_001309832.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	ENST00000254976.7	TSL:1 MANE Select	c.330C>T	p.Asp110Asp	synonymous	Exon 6 of 8	ENSP00000254976.3
	SNAP25	ENST00000304886.6	TSL:1	c.330C>T	p.Asp110Asp	synonymous	Exon 6 of 8	ENSP00000307341.2
	SNAP25	ENST00000961779.1		c.414C>T	p.Asp138Asp	synonymous	Exon 7 of 9	ENSP00000631838.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16630 AN: 152064 Hom.: 1152 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.102

GnomAD2 exomes AF: 0.108 AC: 26980 AN: 250880 AF XY: 0.104

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.0345

Gnomad EAS exome AF: 0.177

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.0667

Gnomad OTH exome AF: 0.0906

GnomAD4 exome AF: 0.0789 AC: 115363 AN: 1461564 Hom.: 5974 Cov.: 31 AF XY: 0.0799 AC XY: 58057 AN XY: 727076

African (AFR) AF: 0.182 AC: 6084 AN: 33458

American (AMR) AF: 0.159 AC: 7106 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.0348 AC: 910 AN: 26130

East Asian (EAS) AF: 0.226 AC: 8959 AN: 39694

South Asian (SAS) AF: 0.128 AC: 11050 AN: 86222

European-Finnish (FIN) AF: 0.131 AC: 7012 AN: 53396

Middle Eastern (MID) AF: 0.0761 AC: 439 AN: 5766

European-Non Finnish (NFE) AF: 0.0620 AC: 68899 AN: 1111832

Other (OTH) AF: 0.0812 AC: 4904 AN: 60390

GnomAD4 genome AF: 0.110 AC: 16670 AN: 152180 Hom.: 1153 Cov.: 33 AF XY: 0.111 AC XY: 8262 AN XY: 74402

African (AFR) AF: 0.176 AC: 7292 AN: 41508

American (AMR) AF: 0.109 AC: 1668 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3472

East Asian (EAS) AF: 0.184 AC: 948 AN: 5160

South Asian (SAS) AF: 0.128 AC: 617 AN: 4826

European-Finnish (FIN) AF: 0.129 AC: 1363 AN: 10598

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0646 AC: 4391 AN: 68012

Other (OTH) AF: 0.101 AC: 214 AN: 2110

Alfa AF: 0.0781 Hom.: 917

Bravo AF: 0.113

Asia WGS AF: 0.159 AC: 553 AN: 3478

EpiCase AF: 0.0595

EpiControl AF: 0.0579

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital myasthenic syndrome 18 (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.5
DANN	Benign	0.89
PhyloP100		0.53
Mutation Taster		=83/17	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: rs362998; hg19: chr20-10277621; COSMIC: COSV54775530; COSMIC: COSV54775530;