20-10306436-G-T

Position:

• chr20-10306436-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.03

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-AS1 (HGNC:44312): (SNAP25 antisense RNA 1)

ACMG classification

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/exons	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.*239G>T		3_prime_UTR_variant	8/8	ENST00000254976.7	NP_570824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7	c.*239G>T		3_prime_UTR_variant	8/8	1	NM_130811.4	ENSP00000254976	P5
SNAP25-AS1	ENST00000421143.6	n.5+62279C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102712 AN: 151426 Hom.: 34919 Cov.: 29

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.: 3 AF XY: 0.664 AC XY: 81229 AN XY: 122386

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.: 29 AF XY: 0.682 AC XY: 50435 AN XY: 73994

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

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

Congenital myasthenic syndrome 18 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

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

Other links and lift over

dbSNP: rs3746544; hg19: chr20-10287084;