Genetic Variant SNAP25:c.*897T>C (chr20-10307094-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_130811.4(SNAP25):c.*897T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,332 control chromosomes in the GnomAD database, including 38,033 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.70 ( 37962 hom., cov: 31)

Exomes 𝑓: 0.71 ( 71 hom. )

Consequence

SNAP25
NM_130811.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72

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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP25	NM_130811.4 link	c.*897T>C		3_prime_UTR_variant	Exon 8 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.*897T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_130811.4	ENSP00000254976.3		P60880-1

Frequencies

GnomAD3 genomes

AF:

0.703

AC:

106837

AN:

151926

Hom.:

37912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.801

Gnomad AMI

AF:

0.589

Gnomad AMR

AF:

0.723

Gnomad ASJ

AF:

0.715

Gnomad EAS

AF:

0.770

Gnomad SAS

AF:

0.724

Gnomad FIN

AF:

0.668

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.640

Gnomad OTH

AF:

0.669

GnomAD4 exome

AF:

0.712

AC:

205

AN:

288

Hom.:

Cov.:

AF XY:

0.736

AC XY:

131

AN XY:

178

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.716

AC:

202

AN:

282

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.703

AC:

106949

AN:

152044

Hom.:

37962

Cov.:

AF XY:

0.707

AC XY:

52529

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.801

AC:

33245

AN:

41486

American (AMR)

AF:

0.723

AC:

11049

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.715

AC:

2482

AN:

3472

East Asian (EAS)

AF:

0.770

AC:

3972

AN:

5158

South Asian (SAS)

AF:

0.723

AC:

3489

AN:

4824

European-Finnish (FIN)

AF:

0.668

AC:

7057

AN:

10560

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.640

AC:

43518

AN:

67952

Other (OTH)

AF:

0.666

AC:

1404

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1601

3202

4804

6405

8006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.663

Hom.:

128885

Bravo

AF:

0.709

Asia WGS

AF:

0.707

AC:

2458

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.5

(source)

DANN

Benign

0.65

PhyloP100

1.7

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

Publications

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20-10307094-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over