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6-147313944-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001127715.4(STXBP5):c.1206C>T(p.Cys402=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000412 in 1,602,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

STXBP5
NM_001127715.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0190
Variant links:
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 -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-147313944-C-T is Benign according to our data. Variant chr6-147313944-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 757956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.019 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
STXBP5NM_001127715.4 linkuse as main transcriptc.1206C>T p.Cys402= synonymous_variant 12/28 ENST00000321680.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
STXBP5ENST00000321680.11 linkuse as main transcriptc.1206C>T p.Cys402= synonymous_variant 12/285 NM_001127715.4 A1Q5T5C0-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000527
AC:
8
AN:
151930
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000867
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000638
AC:
16
AN:
250860
Hom.:
0
AF XY:
0.0000959
AC XY:
13
AN XY:
135588
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.000596
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000400
AC:
58
AN:
1450526
Hom.:
0
Cov.:
30
AF XY:
0.0000485
AC XY:
35
AN XY:
721026
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.000734
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.000237
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000127
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000526
AC:
8
AN:
152046
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000867
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000676
Hom.:
0
Bravo
AF:
0.0000491

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJul 21, 2018- -
STXBP5-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMar 18, 2019This 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.35
Cadd
Benign
9.3
Dann
Benign
0.49
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201944718; hg19: chr6-147635080; API