Genetic Variant SNAP25:c.*239G>T (chr20-10306436-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_130811.4(SNAP25):c.*239G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 389,872 control chromosomes in the GnomAD database, including 87,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 34943 hom., cov: 29)

Exomes 𝑓: 0.66 ( 52578 hom. )

Consequence

SNAP25
NM_130811.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.03

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 20-10306436-G-T is Benign according to our data. Variant chr20-10306436-G-T is described in ClinVar as [Benign]. Clinvar id is 1168327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP25	NM_130811.4 link	c.*239G>T		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.*239G>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_130811.4	ENSP00000254976.3		P60880-1

Frequencies

GnomAD3 genomes

AF:

0.678

AC:

102712

AN:

151426

Hom.:

34919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.719

Gnomad AMI

AF:

0.589

Gnomad AMR

AF:

0.711

Gnomad ASJ

AF:

0.712

Gnomad EAS

AF:

0.770

Gnomad SAS

AF:

0.721

Gnomad FIN

AF:

0.670

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.638

Gnomad OTH

AF:

0.649

GnomAD4 exome

AF:

0.662

AC:

157787

AN:

238328

Hom.:

52578

Cov.:

AF XY:

0.664

AC XY:

81229

AN XY:

122386

show subpopulations

Gnomad4 AFR exome

AF:

0.728

Gnomad4 AMR exome

AF:

0.704

Gnomad4 ASJ exome

AF:

0.703

Gnomad4 EAS exome

AF:

0.735

Gnomad4 SAS exome

AF:

0.706

Gnomad4 FIN exome

AF:

0.667

Gnomad4 NFE exome

AF:

0.642

Gnomad4 OTH exome

AF:

0.662

GnomAD4 genome

AF:

0.678

AC:

102794

AN:

151544

Hom.:

34943

Cov.:

AF XY:

0.682

AC XY:

50435

AN XY:

73994

show subpopulations

Gnomad4 AFR

AF:

0.719

Gnomad4 AMR

AF:

0.711

Gnomad4 ASJ

AF:

0.712

Gnomad4 EAS

AF:

0.770

Gnomad4 SAS

AF:

0.720

Gnomad4 FIN

AF:

0.670

Gnomad4 NFE

AF:

0.638

Gnomad4 OTH

AF:

0.646

Alfa

AF:

0.651

Hom.:

32443

Bravo

AF:

0.681

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 08, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 25650683, 25054019, 26941099) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital myasthenic syndrome 18

Benign:1

Feb 03, 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

-0.65

CADD

Benign

7.1

DANN

Benign

0.69

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