rs1114167275

Positions:

• chr16-31001165-T-TCAATGCACATCC

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_052874.5(STX1B):​c.133_134insGGATGTGCATTG​(p.Lys45delinsArgMetCysIleGlu) variant causes a conservative inframe insertion 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 no classification for the single variant (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: STX1B NM_052874.5 conservative_inframe_insertion
• Clinical Significance: no classification for the single variant no classification for the single variant P:1
• Conservation: PhyloP100: 7.97

Genes affected

STX1B (HGNC:18539): (syntaxin 1B) The protein encoded by this gene belongs to a family of proteins thought to play a role in the exocytosis of synaptic vesicles. Vesicle exocytosis releases vesicular contents and is important to various cellular functions. For instance, the secretion of transmitters from neurons plays an important role in synaptic transmission. After exocytosis, the membrane and proteins from the vesicle are retrieved from the plasma membrane through the process of endocytosis. Mutations in this gene have been identified as one cause of fever-associated epilepsy syndromes. A possible link between this gene and Parkinson's disease has also been suggested. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_052874.5.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX1B	NM_052874.5	c.133_134insGGATGTGCATTG	p.Lys45delinsArgMetCysIleGlu	conservative_inframe_insertion	3/10	ENST00000215095.11	NP_443106.1
STX1B	XM_017022893.2	c.115_116insGGATGTGCATTG	p.Lys39delinsArgMetCysIleGlu	conservative_inframe_insertion	3/10		XP_016878382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX1B	ENST00000215095.11	c.133_134insGGATGTGCATTG	p.Lys45delinsArgMetCysIleGlu	conservative_inframe_insertion	3/10	1	NM_052874.5	ENSP00000215095.5
STX1B	ENST00000565419.2	c.133_134insGGATGTGCATTG	p.Lys45delinsArgMetCysIleGlu	conservative_inframe_insertion	3/9	2		ENSP00000455899.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: no classification for the single variant

Submissions summary: Pathogenic:1

Revision: no classification for the single variant

Submissions by phenotype

Generalized epilepsy with febrile seizures plus, type 9 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1114167275; hg19: chr16-31012486;