20-10275143-C-T

Position:

• chr20-10275143-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_130811.4(SNAP25):​c.-63-286C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 151,794 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.017 (51 hom., cov: 32)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00700

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-10275143-C-T is Benign according to our data. Variant chr20-10275143-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1300470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0168 (2544/151794) while in subpopulation AFR AF= 0.034 (1409/41442). AF 95% confidence interval is 0.0325. There are 51 homozygotes in gnomad4. There are 1232 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2544 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP25	NM_130811.4	c.-63-286C>T		intron_variant		ENST00000254976.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP25	ENST00000254976.7	c.-63-286C>T		intron_variant		1	NM_130811.4	P5
SNAP25-AS1	ENST00000421143.6	n.6-78206G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0167 AC: 2538 AN: 151676 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00546

Gnomad FIN AF: 0.00958

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0100

Gnomad OTH AF: 0.0154

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

GnomAD4 genome AF: 0.0168 AC: 2544 AN: 151794 Hom.: 51 Cov.: 32 AF XY: 0.0166 AC XY: 1232 AN XY: 74182

Gnomad4 AFR AF: 0.0340

Gnomad4 AMR AF: 0.0128

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00567

Gnomad4 FIN AF: 0.00958

Gnomad4 NFE AF: 0.0100

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.0156 Hom.: 5

Bravo AF: 0.0175

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs115753500; hg19: chr20-10255791;