chr20-10296973-C-T

Position:

chr20-10296973-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_130811.4(SNAP25):c.330C>T(p.Asp110=) 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

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 -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/exons	MANE	UniProt
SNAP25	NM_130811.4 linkuse as main transcript	c.330C>T	p.Asp110=	synonymous_variant	6/8	ENST00000254976.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP25	ENST00000254976.7 linkuse as main transcript	c.330C>T	p.Asp110=	synonymous_variant	6/8	1	NM_130811.4	P5	P60880-1
SNAP25-AS1	ENST00000421143.6 linkuse as main transcript	n.5+71742G>A		intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes

AF:

0.108

AC:

26980

AN:

250880

Hom.:

1818

AF XY:

0.104

AC XY:

14094

AN XY:

135600

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 SAS exome

AF:

0.128

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

Gnomad4 AFR exome

AF:

0.182

Gnomad4 AMR exome

AF:

0.159

Gnomad4 ASJ exome

AF:

0.0348

Gnomad4 EAS exome

AF:

0.226

Gnomad4 SAS exome

AF:

0.128

Gnomad4 FIN exome

AF:

0.131

Gnomad4 NFE exome

AF:

0.0620

Gnomad4 OTH exome

AF:

0.0812

GnomAD4 genome

AF:

0.110

AC:

16670

AN:

152180

Hom.:

1153

Cov.:

AF XY:

0.111

AC XY:

8262

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.176

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.0360

Gnomad4 EAS

AF:

0.184

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.129

Gnomad4 NFE

AF:

0.0646

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.0741

Hom.:

665

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 08, 2021	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2016

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.5

DANN

Benign

0.89

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