chr6-147267084-C-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001127715.4(STXBP5):āc.631C>Gā(p.Leu211Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,607,538 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.000027 ( 0 hom. )
Consequence
STXBP5
NM_001127715.4 missense, splice_region
NM_001127715.4 missense, splice_region
Scores
1
10
8
Splicing: ADA: 0.9591
1
1
Clinical Significance
Conservation
PhyloP100: 7.51
Genes affected
STXBP5 (HGNC:19665): (syntaxin binding protein 5) Syntaxin 1 is a component of the 7S and 20S SNARE complexes which are involved in docking and fusion of synaptic vesicles with the presynaptic plasma membrane. This gene encodes a syntaxin 1 binding protein. In rat, a similar protein dissociates syntaxin 1 from the Munc18/n-Sec1/rbSec1 complex to form a 10S complex, an intermediate which can be converted to the 7S SNARE complex. Thus this protein is thought to be involved in neurotransmitter release by stimulating SNARE complex formation. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 40 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STXBP5 | NM_001127715.4 | c.631C>G | p.Leu211Val | missense_variant, splice_region_variant | 7/28 | ENST00000321680.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STXBP5 | ENST00000321680.11 | c.631C>G | p.Leu211Val | missense_variant, splice_region_variant | 7/28 | 5 | NM_001127715.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152054Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000325 AC: 8AN: 245860Hom.: 0 AF XY: 0.0000377 AC XY: 5AN XY: 132768
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GnomAD4 exome AF: 0.0000275 AC: 40AN: 1455484Hom.: 0 Cov.: 30 AF XY: 0.0000290 AC XY: 21AN XY: 723820
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 152054Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74278
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 18, 2023 | The c.631C>G (p.L211V) alteration is located in exon 7 (coding exon 7) of the STXBP5 gene. This alteration results from a C to G substitution at nucleotide position 631, causing the leucine (L) at amino acid position 211 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;L;L
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Benign
T;T;T;T
Polyphen
0.037, 0.028
.;B;B;.
Vest4
MutPred
Gain of methylation at K210 (P = 0.031);Gain of methylation at K210 (P = 0.031);Gain of methylation at K210 (P = 0.031);Gain of methylation at K210 (P = 0.031);
MVP
MPC
0.53
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at