chr20-10296973-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_130811.4(SNAP25):c.330C>T(p.Asp110Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0818 in 1,613,744 control chromosomes in the GnomAD database, including 7,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1153 hom., cov: 33)

Exomes 𝑓: 0.079 ( 5974 hom. )

Consequence

SNAP25
NM_130811.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.528

Publications

27 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 20-10296973-C-T is Benign according to our data. Variant chr20-10296973-C-T is described in ClinVar as [Benign]. Clinvar id is 587804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.528 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP25	NM_130811.4 link	c.330C>T	p.Asp110Asp	synonymous_variant	Exon 6 of 8	ENST00000254976.7	NP_570824.1	P60880-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7 link	c.330C>T	p.Asp110Asp	synonymous_variant	Exon 6 of 8	1	NM_130811.4	ENSP00000254976.3		P60880-1

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16630

AN:

152064

Hom.:

1152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.0360

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0646

Gnomad OTH

AF:

0.102

GnomAD2 exomes

AF:

0.108

AC:

26980

AN:

250880

AF XY:

0.104

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.164

Gnomad ASJ exome

AF:

0.0345

Gnomad EAS exome

AF:

0.177

Gnomad FIN exome

AF:

0.135

Gnomad NFE exome

AF:

0.0667

Gnomad OTH exome

AF:

0.0906

GnomAD4 exome

AF:

0.0789

AC:

115363

AN:

1461564

Hom.:

5974

Cov.:

AF XY:

0.0799

AC XY:

58057

AN XY:

727076

show subpopulations

African (AFR)

AF:

0.182

AC:

6084

AN:

33458

American (AMR)

AF:

0.159

AC:

7106

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.0348

AC:

910

AN:

26130

East Asian (EAS)

AF:

0.226

AC:

8959

AN:

39694

South Asian (SAS)

AF:

0.128

AC:

11050

AN:

86222

European-Finnish (FIN)

AF:

0.131

AC:

7012

AN:

53396

Middle Eastern (MID)

AF:

0.0761

AC:

439

AN:

5766

European-Non Finnish (NFE)

AF:

0.0620

AC:

68899

AN:

1111832

Other (OTH)

AF:

0.0812

AC:

4904

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

5527

11054

16582

22109

27636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2788

5576

8364

11152

13940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.110

AC:

16670

AN:

152180

Hom.:

1153

Cov.:

AF XY:

0.111

AC XY:

8262

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.176

AC:

7292

AN:

41508

American (AMR)

AF:

0.109

AC:

1668

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0360

AC:

125

AN:

3472

East Asian (EAS)

AF:

0.184

AC:

948

AN:

5160

South Asian (SAS)

AF:

0.128

AC:

617

AN:

4826

European-Finnish (FIN)

AF:

0.129

AC:

1363

AN:

10598

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0646

AC:

4391

AN:

68012

Other (OTH)

AF:

0.101

AC:

214

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

736

1472

2207

2943

3679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<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:

0.0781

Hom.:

917

Bravo

AF:

0.113

Asia WGS

AF:

0.159

AC:

553

AN:

3478

EpiCase

AF:

0.0595

EpiControl

AF:

0.0579

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 08, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Jan 08, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Congenital myasthenic syndrome 18

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.5

(source)

DANN

Benign

0.89

PhyloP100

0.53

Mutation Taster

=83/17

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over