20-10265443-A-G

Position:

• chr20-10265443-A-G

Variant summary

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

The ENST00000254976.7(SNAP25):​c.-63-9986A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,240 control chromosomes in the GnomAD database, including 60,411 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 0.89 (60411 hom., cov: 33)
• Consequence: SNAP25 ENST00000254976.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.-63-9986A>G		intron_variant		ENST00000254976.7	NP_570824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7	c.-63-9986A>G		intron_variant		1	NM_130811.4	ENSP00000254976	P5
SNAP25-AS1	ENST00000421143.6	n.6-68506T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135404 AN: 152122 Hom.: 60368 Cov.: 33

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.903

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

GnomAD4 genome AF: 0.890 AC: 135504 AN: 152240 Hom.: 60411 Cov.: 33 AF XY: 0.889 AC XY: 66188 AN XY: 74432

Gnomad4 AFR AF: 0.931

Gnomad4 AMR AF: 0.859

Gnomad4 ASJ AF: 0.923

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.928

Gnomad4 FIN AF: 0.857

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.904

Alfa AF: 0.883 Hom.: 19374

Bravo AF: 0.891

Asia WGS AF: 0.901 AC: 3133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.065
DANN	Benign	0.42

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: rs362567; hg19: chr20-10246091;