NM_130811.4:c.-63-12891G>A

Variant names:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_130811.4(SNAP25):c.-63-12891G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.362 (AC=54,961) in the gnomAD database across 151,862 control chromosomes, including 10,738 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.427. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 10738 hom., cov: 32)

Consequence

SNAP25
NM_130811.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.138

Publications

5 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 Gene-Disease associations (from GenCC):

congenital myasthenic syndrome 18
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: ClinGen, Ambry Genetics
neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
presynaptic congenital myasthenic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SNAP25 links:

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

SNAP25-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_130811.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.4269 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

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

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNAP25	NM_130811.4	MANE Select	c.-63-12891G>A	intron	N/A	NP_570824.1	P60880-1
SNAP25	NM_001322902.2		c.-63-12891G>A	intron	N/A	NP_001309831.1	P60880-2
SNAP25	NM_001322903.2		c.-63-12891G>A	intron	N/A	NP_001309832.1	P60880-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNAP25	ENST00000254976.7	TSL:1 MANE Select	c.-63-12891G>A	intron	N/A	ENSP00000254976.3	P60880-1
SNAP25	ENST00000304886.6	TSL:1	c.-63-12891G>A	intron	N/A	ENSP00000307341.2	P60880-2
SNAP25	ENST00000961779.1		c.-63-12891G>A	intron	N/A	ENSP00000631838.1

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

54938

AN:

151748

Hom.:

10740

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.405

Gnomad ASJ

AF:

0.546

Gnomad EAS

AF:

0.0904

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.431

Gnomad OTH

AF:

0.406

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

GnomAD4 genome

AF:

0.362

AC:

54961

AN:

151862

Hom.:

10738

Cov.:

AF XY:

0.359

AC XY:

26662

AN XY:

74204

show subpopulations

African (AFR)

AF:

0.253

AC:

10504

AN:

41446

American (AMR)

AF:

0.404

AC:

6152

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.546

AC:

1896

AN:

3470

East Asian (EAS)

AF:

0.0906

AC:

465

AN:

5132

South Asian (SAS)

AF:

0.287

AC:

1376

AN:

4802

European-Finnish (FIN)

AF:

0.374

AC:

3942

AN:

10532

Middle Eastern (MID)

AF:

0.534

AC:

157

AN:

294

European-Non Finnish (NFE)

AF:

0.431

AC:

29293

AN:

67954

Other (OTH)

AF:

0.402

AC:

848

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1758

3516

5273

7031

8789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.416

Hom.:

22732

Bravo

AF:

0.359

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.138

AC:

16883

AN:

122552

Turkish Variome

AF:

0.457

AC:

707

AN:

1546

Hom.:

170

ABraOM SABE-WGS-1171

AF:

0.423

AC:

988

AN:

2334

Hom.:

228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.8

(source)

DANN

Benign

0.75

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over