20-10307094-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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.

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.*897T>C		3_prime_UTR	Exon 8 of 8	NP_570824.1
	SNAP25	NM_001322902.2		c.*897T>C		3_prime_UTR	Exon 8 of 8	NP_001309831.1
	SNAP25	NM_001322903.2		c.*897T>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.*897T>C		3_prime_UTR	Exon 8 of 8	ENSP00000254976.3
	SNAP25	ENST00000304886.6	TSL:1	c.*897T>C		3_prime_UTR	Exon 8 of 8	ENSP00000307341.2
	SNAP25	ENST00000495883.1	TSL:2	n.1932T>C		non_coding_transcript_exon	Exon 3 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.716 AC: 202 AN: 282

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.801 AC: 33245 AN: 41486

American (AMR) AF: 0.723 AC: 11049 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2482 AN: 3472

East Asian (EAS) AF: 0.770 AC: 3972 AN: 5158

South Asian (SAS) AF: 0.723 AC: 3489 AN: 4824

European-Finnish (FIN) AF: 0.668 AC: 7057 AN: 10560

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43518 AN: 67952

Other (OTH) AF: 0.666 AC: 1404 AN: 2108

Alfa AF: 0.663 Hom.: 128885

Bravo AF: 0.709

Asia WGS AF: 0.707 AC: 2458 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.65
PhyloP100		1.7
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: rs8636; hg19: chr20-10287742;