chr20-10262538-G-A

Variant names:

• chr20-10262538-G-A
• rs362562
• NM_130811.4:c.-63-12891G>A

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_130811.4(SNAP25):c.-63-12891G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.362 (AC=54,961) in the gnomAD database across 151,862 control chromosomes, including 10,738 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.427. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10738 hom., cov: 32)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 5 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 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 18

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: ClinGen, Ambry Genetics
• neurodevelopmental disorder

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SNAP25-AS1 (HGNC:44312): (SNAP25 antisense RNA 1) Predicted to be involved in SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition. Predicted to be part of signal recognition particle, endoplasmic reticulum targeting. [provided by Alliance of Genome Resources, Jul 2025]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.4269 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_130811.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	SNAP25 NM_130811.4	MANE Select	c.-63-12891G>A	intron	Intron 1 of 7	Prot: NP_570824.1 UniProt:
	SNAP25 NM_001322902.2		c.-63-12891G>A	intron	Intron 1 of 7	Prot: NP_001309831.1 UniProt:
	SNAP25 NM_001322903.2		c.-63-12891G>A	intron	Intron 2 of 8	Prot: NP_001309832.1 UniProt:

SNAP25 NM_130811.4

MANE Select

HGVSc / HGVSpc.-63-12891G>A

Exon rankIntron 1 of 7

intron

Prot: NP_570824.1UniProt: P60880-1

SNAP25 NM_001322902.2

HGVSc / HGVSpc.-63-12891G>A

Exon rankIntron 1 of 7

intron

Prot: NP_001309831.1UniProt: P60880-2

SNAP25 NM_001322903.2

HGVSc / HGVSpc.-63-12891G>A

Exon rankIntron 2 of 8

intron

Prot: NP_001309832.1UniProt: P60880-1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	SNAP25 ENST00000254976.7	TSL:1MANE Select	c.-63-12891G>A	intron	Intron 1 of 7	Prot: ENSP00000254976.3 UniProt:
	SNAP25 ENST00000304886.6	TSL:1	c.-63-12891G>A	intron	Intron 1 of 7	Prot: ENSP00000307341.2 UniProt:
	SNAP25 ENST00000961779.1		c.-63-12891G>A	intron	Intron 1 of 8	Prot: ENSP00000631838.1 UniProt:

SNAP25 ENST00000254976.7

TSL:1MANE Select

HGVSc / HGVSpc.-63-12891G>A

Exon rankIntron 1 of 7

intron

Prot: ENSP00000254976.3UniProt: P60880-1

SNAP25 ENST00000304886.6

TSL:1

HGVSc / HGVSpc.-63-12891G>A

Exon rankIntron 1 of 7

intron

Prot: ENSP00000307341.2UniProt: P60880-2

SNAP25 ENST00000961779.1

HGVSc / HGVSpc.-63-12891G>A

Exon rankIntron 1 of 8

intron

Prot: ENSP00000631838.1UniProt: A0ACI8V5C3

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.362	AC:54938	Hom:10740	AN:151748	Cov:32
GnomAD4 genome	AF: 0.362	AC:54961	Hom:10738	AN:151862	Cov:32
TOPMed (Bravo)	AF: 0.359	AC:95068	Hom:18567	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.414	AC:114614	Hom:24178	AN:277014	Cov:
Local & regional cohorts 8 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.423	AC:988	Hom:228	AN:2334	Cov:
ChinaMAP Phase 1	AF: 0.0961	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.447	AC:134	Hom:	AN:300	Cov:
Korea4K (4,157 Koreans)	AF: 0.118	AC:854	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.648	AC:114	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.138	AC:16883	Hom:1167	AN:122552	Cov:
Turkish Variome	AF: 0.457	AC:707	Hom:170	AN:1546	Cov:
UK10K	AF: 0.409	AC:3093	Hom:	AN:7562	Cov:

Showing 12 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	9.2
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.75
GPN-Star LLR	N/A	2.3
GPN-Star score	N/A	-1.9
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	0.14

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs362562;

hg19: chr20-10243186;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar