rs363050

chr20-10253609-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_130811.4(SNAP25):c.-63-21820G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,910 control chromosomes in the GnomAD database, including 24,456 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.56 (24456 hom., cov: 31)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.230

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-10253609-G-A is Benign according to our data. Variant chr20-10253609-G-A is described in ClinVar as [Benign]. Clinvar id is 542731.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP25	NM_130811.4	c.-63-21820G>A		intron_variant		ENST00000254976.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP25	ENST00000254976.7	c.-63-21820G>A		intron_variant		1	NM_130811.4	P5
SNAP25-AS1	ENST00000421143.6	n.6-56672C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85316 AN: 151792 Hom.: 24435 Cov.: 31

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.562 AC: 85390 AN: 151910 Hom.: 24456 Cov.: 31 AF XY: 0.553 AC XY: 41053 AN XY: 74212

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.557

Alfa AF: 0.555 Hom.: 8608

Bravo AF: 0.566

Asia WGS AF: 0.415 AC: 1444 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital myasthenic syndrome 18 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.3
Dann	Benign	0.32

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: rs363050; hg19: chr20-10234257;