chr6-147267146-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2
The NM_001127715.4(STXBP5):c.693C>T(p.Asp231=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,609,994 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 1 hom. )
Consequence
STXBP5
NM_001127715.4 synonymous
NM_001127715.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.94
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 Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant 6-147267146-C-T is Benign according to our data. Variant chr6-147267146-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042400.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=2.93 with no splicing effect.
BS2
High AC in GnomAd4 at 36 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STXBP5 | NM_001127715.4 | c.693C>T | p.Asp231= | synonymous_variant | 7/28 | ENST00000321680.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STXBP5 | ENST00000321680.11 | c.693C>T | p.Asp231= | synonymous_variant | 7/28 | 5 | NM_001127715.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 152092Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000407 AC: 101AN: 248128Hom.: 0 AF XY: 0.000424 AC XY: 57AN XY: 134288
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GnomAD4 exome AF: 0.000226 AC: 330AN: 1457784Hom.: 1 Cov.: 30 AF XY: 0.000234 AC XY: 170AN XY: 725222
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GnomAD4 genome AF: 0.000237 AC: 36AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74418
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
STXBP5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 24, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at