20-10231564-T-C

Variant names:

• chr20-10231564-T-C
• rs2423486
• NM_130811.4:c.-64+12587T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130811.4(SNAP25):​c.-64+12587T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,988 control chromosomes in the GnomAD database, including 36,092 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 0.66 (36082 hom., cov: 31)
  • Exomes 𝑓: 0.74 (10 hom.)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.886
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.-64+12587T>C		intron_variant	Intron 1 of 7	ENST00000254976.7	NP_570824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7	c.-64+12587T>C		intron_variant	Intron 1 of 7	1	NM_130811.4	ENSP00000254976.3

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100491 AN: 151834 Hom.: 36073 Cov.: 31

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.714

GnomAD4 exome AF: 0.735 AC: 25 AN: 34 Hom.: 10 Cov.: 0 AF XY: 0.821 AC XY: 23 AN XY: 28

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.625 AC: 15 AN: 24

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.662 AC: 100539 AN: 151954 Hom.: 36082 Cov.: 31 AF XY: 0.666 AC XY: 49471 AN XY: 74258

African (AFR) AF: 0.351 AC: 14527 AN: 41414

American (AMR) AF: 0.781 AC: 11921 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2692 AN: 3468

East Asian (EAS) AF: 0.717 AC: 3682 AN: 5132

South Asian (SAS) AF: 0.780 AC: 3753 AN: 4812

European-Finnish (FIN) AF: 0.758 AC: 8026 AN: 10584

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.786 AC: 53441 AN: 67966

Other (OTH) AF: 0.716 AC: 1507 AN: 2104

Alfa AF: 0.700 Hom.: 4687

Bravo AF: 0.650

Asia WGS AF: 0.750 AC: 2606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.81
PhyloP100		0.89
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2423486; hg19: chr20-10212212;