chr20-10275541-GGGCTGACCAGTT-G

Position:

• chr20-10275541-GGGCTGACCAGTT-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 7P and 2B. PM1 PM2 PM4 PP3 BP6_Moderate

The NM_130811.4(SNAP25):​c.57_68del​(p.Gln20_Asp23del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R17R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNAP25 NM_130811.4 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 9.20

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 Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a helix (size 72) in uniprot entity SNP25_HUMAN there are 11 pathogenic changes around while only 3 benign (79%) in NM_130811.4
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_130811.4.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• BP6: Variant 20-10275541-GGGCTGACCAGTT-G is Benign according to our data. Variant chr20-10275541-GGGCTGACCAGTT-G is described in ClinVar as [Likely_benign]. Clinvar id is 1390252.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP25	NM_130811.4	c.57_68del	p.Gln20_Asp23del	inframe_deletion	2/8	ENST00000254976.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP25	ENST00000254976.7	c.57_68del	p.Gln20_Asp23del	inframe_deletion	2/8	1	NM_130811.4	P5
SNAP25-AS1	ENST00000421143.6	n.6-78616_6-78605del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital myasthenic syndrome 18 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 17, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-10256189;