Variant 20-10275458-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_130811.4(SNAP25):c.-34C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0048 in 1,576,874 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0049 ( 47 hom. )

Consequence

SNAP25
NM_130811.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.146

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 20-10275458-C-A is Benign according to our data. Variant chr20-10275458-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1301162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00353 (538/152328) while in subpopulation SAS AF= 0.0209 (101/4822). AF 95% confidence interval is 0.0176. There are 10 homozygotes in gnomad4. There are 267 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 538 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP25	NM_130811.4 linkuse as main transcript	c.-34C>A		5_prime_UTR_variant	2/8	ENST00000254976.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP25	ENST00000254976.7 linkuse as main transcript	c.-34C>A		5_prime_UTR_variant	2/8	1	NM_130811.4	P5	P60880-1
SNAP25-AS1	ENST00000421143.6 linkuse as main transcript	n.6-78521G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00353

AC:

537

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0209

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00411

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00477

AC:

958

AN:

200878

Hom.:

AF XY:

0.00575

AC XY:

617

AN XY:

107348

show subpopulations

Gnomad AFR exome

AF:

0.000729

Gnomad AMR exome

AF:

0.00222

Gnomad ASJ exome

AF:

0.0154

Gnomad EAS exome

AF:

0.000132

Gnomad SAS exome

AF:

0.0170

Gnomad FIN exome

AF:

0.000282

Gnomad NFE exome

AF:

0.00323

Gnomad OTH exome

AF:

0.00492

GnomAD4 exome

AF:

0.00494

AC:

7031

AN:

1424546

Hom.:

Cov.:

AF XY:

0.00535

AC XY:

3777

AN XY:

705504

show subpopulations

Gnomad4 AFR exome

AF:

0.000820

Gnomad4 AMR exome

AF:

0.00200

Gnomad4 ASJ exome

AF:

0.0143

Gnomad4 EAS exome

AF:

0.0000519

Gnomad4 SAS exome

AF:

0.0175

Gnomad4 FIN exome

AF:

0.000196

Gnomad4 NFE exome

AF:

0.00430

Gnomad4 OTH exome

AF:

0.00670

GnomAD4 genome

AF:

0.00353

AC:

538

AN:

152328

Hom.:

Cov.:

AF XY:

0.00358

AC XY:

267

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0209

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00413

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00399

Hom.:

Bravo

AF:

0.00305

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 08, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.8

DANN

Benign

0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over