rs6039769

Variant names:

• chr20-10218306-A-C
• rs6039769
• ENST00000808220.1:n.98T>G

Your query was ambiguous. Multiple possible variants found:

• chr20-10218306-A-C
• chr20-10218306-A-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000808220.1(ENSG00000305058):​n.98T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 151,816 control chromosomes in the GnomAD database, including 45,503 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 0.77 (45503 hom., cov: 29)
• Consequence: ENSG00000305058 ENST00000808220.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.678
• Publications: 16 publications found

Genes affected

ENSG00000305058 (HGNC:):

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

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 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, ClinGen
• congenital myasthenic syndrome 18

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• presynaptic congenital myasthenic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000808220.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25-AS1	NR_040710.1		n.270+931T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000305058	ENST00000808220.1		n.98T>G		non_coding_transcript_exon	Exon 1 of 1
	SNAP25-AS1	ENST00000421143.7	TSL:5	n.133-21369T>G		intron	N/A
	SNAP25-AS1	ENST00000426491.5	TSL:5	n.270+931T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116180 AN: 151698 Hom.: 45444 Cov.: 29

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.748

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.766 AC: 116300 AN: 151816 Hom.: 45503 Cov.: 29 AF XY: 0.771 AC XY: 57170 AN XY: 74160

African (AFR) AF: 0.936 AC: 38815 AN: 41448

American (AMR) AF: 0.780 AC: 11925 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2542 AN: 3472

East Asian (EAS) AF: 0.767 AC: 3914 AN: 5100

South Asian (SAS) AF: 0.731 AC: 3505 AN: 4796

European-Finnish (FIN) AF: 0.729 AC: 7664 AN: 10506

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45623 AN: 67904

Other (OTH) AF: 0.748 AC: 1573 AN: 2104

Alfa AF: 0.693 Hom.: 54007

Bravo AF: 0.777

Asia WGS AF: 0.767 AC: 2665 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Benign	0.77
PhyloP100		0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6039769;

hg19: chr20-10198954;