rs201770060
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 3P and 8B. PM1PP2BP4_ModerateBP6_ModerateBS2
The NM_130811.4(SNAP25):c.13G>A(p.Ala5Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000804 in 1,604,686 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 Benign (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000083 ( 0 hom. )
Consequence
SNAP25
NM_130811.4 missense
NM_130811.4 missense
Scores
2
3
14
Clinical Significance
Conservation
PhyloP100: 7.33
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM1
?
In a region_of_interest Interaction with CENPF (size 74) in uniprot entity SNP25_HUMAN there are 11 pathogenic changes around while only 4 benign (73%) in NM_130811.4
PP2
?
Missense variant where missense usually causes diseases, SNAP25
BP4
?
Computational evidence support a benign effect (MetaRNN=0.16318989).
BP6
?
Variant 20-10275504-G-A is Benign according to our data. Variant chr20-10275504-G-A is described in ClinVar as [Benign]. Clinvar id is 576987.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SNAP25 | NM_130811.4 | c.13G>A | p.Ala5Thr | missense_variant | 2/8 | ENST00000254976.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SNAP25 | ENST00000254976.7 | c.13G>A | p.Ala5Thr | missense_variant | 2/8 | 1 | NM_130811.4 | P5 | |
SNAP25-AS1 | ENST00000421143.6 | n.6-78567C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152220Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000796 AC: 19AN: 238666Hom.: 0 AF XY: 0.0000778 AC XY: 10AN XY: 128572
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GnomAD4 exome AF: 0.0000833 AC: 121AN: 1452466Hom.: 0 Cov.: 30 AF XY: 0.0000887 AC XY: 64AN XY: 721590
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74358
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital myasthenic syndrome 18 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;B;.
Vest4
MutPred
Gain of phosphorylation at A5 (P = 0.0103);Gain of phosphorylation at A5 (P = 0.0103);Gain of phosphorylation at A5 (P = 0.0103);
MVP
MPC
ClinPred
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at