rs1114167275

Variant names:

• chr16-31001165-T-TCAATGCACATCC
• rs1114167275
• NM_052874.5:c.133_134insGGATGTGCATTG

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. 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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 1 publications found

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]

STX1B Gene-Disease associations (from GenCC):

• generalized epilepsy with febrile seizures plus

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• generalized epilepsy with febrile seizures plus, type 9

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• 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 rank	MANE	Protein	UniProt
STX1B	NM_052874.5	c.133_134insGGATGTGCATTG	p.Lys45delinsArgMetCysIleGlu	conservative_inframe_insertion	Exon 3 of 10	ENST00000215095.11	NP_443106.1
STX1B	XM_017022893.2	c.115_116insGGATGTGCATTG	p.Lys39delinsArgMetCysIleGlu	conservative_inframe_insertion	Exon 3 of 10		XP_016878382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX1B	ENST00000215095.11	c.133_134insGGATGTGCATTG	p.Lys45delinsArgMetCysIleGlu	conservative_inframe_insertion	Exon 3 of 10	1	NM_052874.5	ENSP00000215095.5
STX1B	ENST00000565419.2	c.133_134insGGATGTGCATTG	p.Lys45delinsArgMetCysIleGlu	conservative_inframe_insertion	Exon 3 of 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

Dec 01, 2014

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0
Mutation Taster		=2/198	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs1114167275; hg19: chr16-31012486;