Genetic Variant SNAP25:p.Arg16Gln (chr20-10275538-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_130811.4(SNAP25):c.47G>A(p.Arg16Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SNAP25
NM_130811.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88

Publications

2 publications found

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 links:

SNAP25-AS1 (HGNC:44312): (SNAP25 antisense RNA 1)

SNAP25-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14385557).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130811.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNAP25	NM_130811.4	MANE Select	c.47G>A	p.Arg16Gln	missense	Exon 2 of 8	NP_570824.1	P60880-1
SNAP25	NM_001322902.2		c.47G>A	p.Arg16Gln	missense	Exon 2 of 8	NP_001309831.1	P60880-2
SNAP25	NM_001322903.2		c.47G>A	p.Arg16Gln	missense	Exon 3 of 9	NP_001309832.1	P60880-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNAP25	ENST00000254976.7	TSL:1 MANE Select	c.47G>A	p.Arg16Gln	missense	Exon 2 of 8	ENSP00000254976.3	P60880-1
SNAP25	ENST00000304886.6	TSL:1	c.47G>A	p.Arg16Gln	missense	Exon 2 of 8	ENSP00000307341.2	P60880-2
SNAP25	ENST00000961779.1		c.47G>A	p.Arg16Gln	missense	Exon 2 of 9	ENSP00000631838.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000417

AC:

AN:

239888

AF XY:

0.00000774

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000562

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1450808

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720984

African (AFR)

AF:

0.00

AC:

AN:

33336

American (AMR)

AF:

0.00

AC:

AN:

43810

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25846

East Asian (EAS)

AF:

0.00

AC:

AN:

39454

South Asian (SAS)

AF:

0.00

AC:

AN:

83768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106026

Other (OTH)

AF:

0.00

AC:

AN:

59884

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital myasthenic syndrome 18 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Benign

-0.13

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0020

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

PhyloP100

4.9

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.30

REVEL

Benign

0.13

Sift

Benign

0.35

Sift4G

Benign

0.38

Polyphen

0.0010

Vest4

0.33

MutPred

0.35

Loss of MoRF binding (P = 0.0974)

MVP

0.20

MPC

0.12

ClinPred

0.38

GERP RS

6.1

Varity_R

0.44

gMVP

0.65

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over