chr20-10301379-C-T

Variant names:

• chr20-10301379-C-T
• rs6039820
• NM_130811.4:c.552+1967C>T

Variant summary

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

The NM_130811.4(SNAP25):​c.552+1967C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 152,022 control chromosomes in the GnomAD database, including 29,122 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 0.60 (29122 hom., cov: 32)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 11 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 = 0.816 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.552+1967C>T		intron	N/A	NP_570824.1
	SNAP25	NM_001322902.2		c.552+1967C>T		intron	N/A	NP_001309831.1
	SNAP25	NM_001322903.2		c.552+1967C>T		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.552+1967C>T		intron	N/A	ENSP00000254976.3
	SNAP25	ENST00000304886.6	TSL:1	c.552+1967C>T		intron	N/A	ENSP00000307341.2
	SNAP25	ENST00000685131.1		c.552+1967C>T		intron	N/A	ENSP00000508837.1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91350 AN: 151904 Hom.: 29066 Cov.: 32

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.602 AC: 91473 AN: 152022 Hom.: 29122 Cov.: 32 AF XY: 0.605 AC XY: 44972 AN XY: 74306

African (AFR) AF: 0.823 AC: 34147 AN: 41488

American (AMR) AF: 0.603 AC: 9216 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2066 AN: 3470

East Asian (EAS) AF: 0.620 AC: 3214 AN: 5180

South Asian (SAS) AF: 0.599 AC: 2879 AN: 4810

European-Finnish (FIN) AF: 0.528 AC: 5568 AN: 10552

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.479 AC: 32568 AN: 67930

Other (OTH) AF: 0.576 AC: 1217 AN: 2112

Alfa AF: 0.526 Hom.: 72901

Bravo AF: 0.618

Asia WGS AF: 0.618 AC: 2150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.30
PhyloP100		-0.25
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: rs6039820; hg19: chr20-10282027;