rs6077699

Variant names:

• chr20-10243658-A-C
• rs6077699
• NM_130811.4:c.-64+24681A>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.-64+24681A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,006 control chromosomes in the GnomAD database, including 6,605 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 0.29 (6605 hom., cov: 32)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 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.-64+24681A>C		intron	N/A	NP_570824.1	P60880-1
	SNAP25	NM_001322902.2		c.-64+24445A>C		intron	N/A	NP_001309831.1	P60880-2
	SNAP25	NM_001322903.2		c.-64+9321A>C		intron	N/A	NP_001309832.1	P60880-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	ENST00000254976.7	TSL:1 MANE Select	c.-64+24681A>C		intron	N/A	ENSP00000254976.3	P60880-1
	SNAP25	ENST00000304886.6	TSL:1	c.-64+24681A>C		intron	N/A	ENSP00000307341.2	P60880-2
	SNAP25	ENST00000961779.1		c.-64+24681A>C		intron	N/A	ENSP00000631838.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43938 AN: 151886 Hom.: 6600 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.0475

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.289 AC: 43983 AN: 152006 Hom.: 6605 Cov.: 32 AF XY: 0.284 AC XY: 21067 AN XY: 74290

African (AFR) AF: 0.309 AC: 12789 AN: 41410

American (AMR) AF: 0.295 AC: 4511 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1332 AN: 3468

East Asian (EAS) AF: 0.0478 AC: 248 AN: 5190

South Asian (SAS) AF: 0.263 AC: 1267 AN: 4814

European-Finnish (FIN) AF: 0.192 AC: 2029 AN: 10580

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.307 AC: 20864 AN: 67968

Other (OTH) AF: 0.302 AC: 636 AN: 2106

Alfa AF: 0.306 Hom.: 8763

Bravo AF: 0.293

Asia WGS AF: 0.166 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.70
PhyloP100		-0.49
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: rs6077699; hg19: chr20-10224306;