rs724159974
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP2PP3PP5
The ENST00000215095.11(STX1B):c.647T>A(p.Val216Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
STX1B
ENST00000215095.11 missense
ENST00000215095.11 missense
Scores
6
7
6
Clinical Significance
Conservation
PhyloP100: 8.95
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM1
In a domain t-SNARE coiled-coil homology (size 62) in uniprot entity STX1B_HUMAN there are 6 pathogenic changes around while only 2 benign (75%) in ENST00000215095.11
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), STX1B. . Gene score misZ 2.9426 (greater than the threshold 3.09). Trascript score misZ 3.6025 (greater than threshold 3.09). GenCC has associacion of gene with generalized epilepsy with febrile seizures plus, generalized epilepsy with febrile seizures plus, type 9.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.81
PP5
Variant 16-30993375-A-T is Pathogenic according to our data. Variant chr16-30993375-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 162398.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STX1B | NM_052874.5 | c.647T>A | p.Val216Glu | missense_variant | 8/10 | ENST00000215095.11 | NP_443106.1 | |
STX1B | XM_017022893.2 | c.629T>A | p.Val210Glu | missense_variant | 8/10 | XP_016878382.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STX1B | ENST00000215095.11 | c.647T>A | p.Val216Glu | missense_variant | 8/10 | 1 | NM_052874.5 | ENSP00000215095 | P1 | |
STX1B | ENST00000565419.2 | c.647T>A | p.Val216Glu | missense_variant | 8/9 | 2 | ENSP00000455899 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
B;.
Vest4
MutPred
Loss of catalytic residue at V216 (P = 0.0058);Loss of catalytic residue at V216 (P = 0.0058);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at