NM_130811.4:c.*239G>T

Variant names:

• chr20-10306436-G-T
• rs3746544
• NM_130811.4:c.*239G>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.*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
• Publications: 101 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=-0.65).
• BP6: Variant 20-10306436-G-T is Benign according to our data. Variant chr20-10306436-G-T is described in ClinVar as Benign. ClinVar VariationId 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.

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.*239G>T		3_prime_UTR	Exon 8 of 8	NP_570824.1	P60880-1
	SNAP25	NM_001322902.2		c.*239G>T		3_prime_UTR	Exon 8 of 8	NP_001309831.1	P60880-2
	SNAP25	NM_001322903.2		c.*239G>T		3_prime_UTR	Exon 9 of 9	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.*239G>T		3_prime_UTR	Exon 8 of 8	ENSP00000254976.3	P60880-1
	SNAP25	ENST00000304886.6	TSL:1	c.*239G>T		3_prime_UTR	Exon 8 of 8	ENSP00000307341.2	P60880-2
	SNAP25	ENST00000961779.1		c.*239G>T		3_prime_UTR	Exon 9 of 9	ENSP00000631838.1

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

African (AFR) AF: 0.728 AC: 4832 AN: 6634

American (AMR) AF: 0.704 AC: 5496 AN: 7802

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 5989 AN: 8524

East Asian (EAS) AF: 0.735 AC: 15032 AN: 20440

South Asian (SAS) AF: 0.706 AC: 5724 AN: 8104

European-Finnish (FIN) AF: 0.667 AC: 14306 AN: 21458

Middle Eastern (MID) AF: 0.655 AC: 789 AN: 1204

European-Non Finnish (NFE) AF: 0.642 AC: 95493 AN: 148856

Other (OTH) AF: 0.662 AC: 10126 AN: 15306

GnomAD4 genome AF: 0.678 AC: 102794 AN: 151544 Hom.: 34943 Cov.: 29 AF XY: 0.682 AC XY: 50435 AN XY: 73994

African (AFR) AF: 0.719 AC: 29696 AN: 41310

American (AMR) AF: 0.711 AC: 10806 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2467 AN: 3464

East Asian (EAS) AF: 0.770 AC: 3964 AN: 5150

South Asian (SAS) AF: 0.720 AC: 3449 AN: 4788

European-Finnish (FIN) AF: 0.670 AC: 7016 AN: 10478

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43310 AN: 67858

Other (OTH) AF: 0.646 AC: 1358 AN: 2102

Alfa AF: 0.656 Hom.: 91669

Bravo AF: 0.681

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital myasthenic syndrome 18 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.1
DANN	Benign	0.69
PhyloP100		1.0
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: rs3746544; hg19: chr20-10287084;