NM_130811.4:c.-63-11451T>C

Variant names:

• chr20-10263978-T-C
• rs362564
• NM_130811.4:c.-63-11451T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_130811.4(SNAP25):​c.-63-11451T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,922 control chromosomes in the GnomAD database, including 12,348 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12348 hom., cov: 31)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.-63-11451T>C		intron_variant	Intron 1 of 7	ENST00000254976.7	NP_570824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7	c.-63-11451T>C		intron_variant	Intron 1 of 7	1	NM_130811.4	ENSP00000254976.3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60697 AN: 151806 Hom.: 12362 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.400

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.400 AC: 60703 AN: 151922 Hom.: 12348 Cov.: 31 AF XY: 0.401 AC XY: 29786 AN XY: 74198

African (AFR) AF: 0.360 AC: 14921 AN: 41422

American (AMR) AF: 0.376 AC: 5741 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1265 AN: 3470

East Asian (EAS) AF: 0.615 AC: 3169 AN: 5152

South Asian (SAS) AF: 0.559 AC: 2694 AN: 4818

European-Finnish (FIN) AF: 0.404 AC: 4255 AN: 10532

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.400 AC: 27206 AN: 67956

Other (OTH) AF: 0.405 AC: 855 AN: 2112

Alfa AF: 0.382 Hom.: 6911

Bravo AF: 0.393

Asia WGS AF: 0.587 AC: 2042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.89
PhyloP100		2.1
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: rs362564; hg19: chr20-10244626;