20-10307094-T-C

Variant names:

• chr20-10307094-T-C
• rs8636
• NM_130811.4:c.*897T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130811.4(SNAP25):​c.*897T>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 0.703 in 152,332 control chromosomes in the GnomAD database, including 38,033 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 0.70 (37962 hom., cov: 31)
  • Exomes 𝑓: 0.71 (71 hom.)
• Consequence: SNAP25 NM_130811.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.*897T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000254976.7	NP_570824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7	c.*897T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_130811.4	ENSP00000254976.3

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106837 AN: 151926 Hom.: 37912 Cov.: 31

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.669

GnomAD4 exome AF: 0.712 AC: 205 AN: 288 Hom.: 71 Cov.: 0 AF XY: 0.736 AC XY: 131 AN XY: 178

Gnomad4 FIN exome AF: 0.716

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.703 AC: 106949 AN: 152044 Hom.: 37962 Cov.: 31 AF XY: 0.707 AC XY: 52529 AN XY: 74338

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.666

Alfa AF: 0.657 Hom.: 56355

Bravo AF: 0.709

Asia WGS AF: 0.707 AC: 2458 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.65

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: rs8636; hg19: chr20-10287742;