20-10275503-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_130811.4(SNAP25):​c.12C>T​(p.Asp4Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,452,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SNAP25
NM_130811.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.509
Variant links:
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)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.21).
BP6
Variant 20-10275503-C-T is Benign according to our data. Variant chr20-10275503-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1590536.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.509 with no splicing effect.
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNAP25NM_130811.4 linkc.12C>T p.Asp4Asp synonymous_variant 2/8 ENST00000254976.7 NP_570824.1 P60880-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNAP25ENST00000254976.7 linkc.12C>T p.Asp4Asp synonymous_variant 2/81 NM_130811.4 ENSP00000254976.3 P60880-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000413
AC:
6
AN:
1452692
Hom.:
0
Cov.:
30
AF XY:
0.00000693
AC XY:
5
AN XY:
721740
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000229
Gnomad4 ASJ exome
AF:
0.0000386
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000181
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Congenital myasthenic syndrome 18 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 11, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.21
CADD
Benign
11
DANN
Benign
0.86

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs769285280; hg19: chr20-10256151; API