rs79020892

Variant names:

• chr20-10306125-C-T
• rs79020892
• NM_130811.4:c.553-4C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130811.4(SNAP25):​c.553-4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,613,448 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (77 hom., cov: 30)
  • Exomes 𝑓: 0.0019 (55 hom.)
• Consequence: SNAP25 NM_130811.4 splice_region, intron
• Scores: Splicing: ADA: 0.0004871
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.445
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 20-10306125-C-T is Benign according to our data. Variant chr20-10306125-C-T is described in ClinVar as Benign. ClinVar VariationId is 476115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130811.4. 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	NM_130811.4	MANE Select	c.553-4C>T		splice_region intron	N/A	NP_570824.1	P60880-1
	SNAP25	NM_001322902.2		c.553-4C>T		splice_region intron	N/A	NP_001309831.1	P60880-2
	SNAP25	NM_001322903.2		c.553-4C>T		splice_region intron	N/A	NP_001309832.1	P60880-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	ENST00000254976.7	TSL:1 MANE Select	c.553-4C>T		splice_region intron	N/A	ENSP00000254976.3	P60880-1
	SNAP25	ENST00000304886.6	TSL:1	c.553-4C>T		splice_region intron	N/A	ENSP00000307341.2	P60880-2
	SNAP25	ENST00000961779.1		c.637-4C>T		splice_region intron	N/A	ENSP00000631838.1

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2511 AN: 151952 Hom.: 77 Cov.: 30

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00767

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00426 AC: 1069 AN: 251166 AF XY: 0.00345

Gnomad AFR exome AF: 0.0562

Gnomad AMR exome AF: 0.00299

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00187 AC: 2735 AN: 1461378 Hom.: 55 Cov.: 30 AF XY: 0.00165 AC XY: 1200 AN XY: 726978

African (AFR) AF: 0.0595 AC: 1990 AN: 33432

American (AMR) AF: 0.00372 AC: 166 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5762

European-Non Finnish (NFE) AF: 0.000282 AC: 314 AN: 1111702

Other (OTH) AF: 0.00393 AC: 237 AN: 60370

GnomAD4 genome AF: 0.0166 AC: 2518 AN: 152070 Hom.: 77 Cov.: 30 AF XY: 0.0169 AC XY: 1253 AN XY: 74344

African (AFR) AF: 0.0565 AC: 2343 AN: 41452

American (AMR) AF: 0.00766 AC: 117 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 67976

Other (OTH) AF: 0.0119 AC: 25 AN: 2102

Alfa AF: 0.0106 Hom.: 28

Bravo AF: 0.0184

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000546

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Congenital myasthenic syndrome 18 (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00049
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.020		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: rs79020892; hg19: chr20-10286773;