chr20-10263978-T-C

Position:

• chr20-10263978-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_130811.4(SNAP25):​c.-63-11451T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,922 control chromosomes in the GnomAD database, including 12,348 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 0.40 (12348 hom., cov: 31)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.-63-11451T>C		intron_variant		ENST00000254976.7	NP_570824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7	c.-63-11451T>C		intron_variant		1	NM_130811.4	ENSP00000254976	P5
SNAP25-AS1	ENST00000421143.6	n.6-67041A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60697 AN: 151806 Hom.: 12362 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.400 AC: 60703 AN: 151922 Hom.: 12348 Cov.: 31 AF XY: 0.401 AC XY: 29786 AN XY: 74198

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.405

Alfa AF: 0.381 Hom.: 6227

Bravo AF: 0.393

Asia WGS AF: 0.587 AC: 2042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.89

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: rs362564; hg19: chr20-10244626;