rs6039783

Variant names:

• chr20-10237386-T-C
• rs6039783
• NM_130811.4:c.-64+18409T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000254976.7(SNAP25):​c.-64+18409T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,136 control chromosomes in the GnomAD database, including 2,941 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 0.14 (2941 hom., cov: 32)
• Consequence: SNAP25 ENST00000254976.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000254976.7. 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.-64+18409T>C		intron	N/A	NP_570824.1
	SNAP25	NM_001322902.2		c.-64+18173T>C		intron	N/A	NP_001309831.1
	SNAP25	NM_001322903.2		c.-64+3049T>C		intron	N/A	NP_001309832.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	ENST00000254976.7	TSL:1 MANE Select	c.-64+18409T>C		intron	N/A	ENSP00000254976.3
	SNAP25	ENST00000304886.6	TSL:1	c.-64+18409T>C		intron	N/A	ENSP00000307341.2
	SNAP25	ENST00000685131.1		c.-83-621T>C		intron	N/A	ENSP00000508837.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21709 AN: 152018 Hom.: 2938 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.0757

Gnomad EAS AF: 0.0739

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.0442

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0580

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.143 AC: 21750 AN: 152136 Hom.: 2941 Cov.: 32 AF XY: 0.140 AC XY: 10399 AN XY: 74380

African (AFR) AF: 0.361 AC: 14957 AN: 41436

American (AMR) AF: 0.0749 AC: 1146 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0757 AC: 262 AN: 3462

East Asian (EAS) AF: 0.0744 AC: 385 AN: 5172

South Asian (SAS) AF: 0.0541 AC: 261 AN: 4824

European-Finnish (FIN) AF: 0.0442 AC: 469 AN: 10618

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0580 AC: 3945 AN: 68008

Other (OTH) AF: 0.121 AC: 256 AN: 2114

Alfa AF: 0.0914 Hom.: 3351

Bravo AF: 0.156

Asia WGS AF: 0.0730 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.64
PhyloP100		-0.045
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: rs6039783; hg19: chr20-10218034;