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GeneBe

6-147204527-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The ENST00000546097.5(STXBP5):c.103G>A(p.Glu35Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00179 in 1,611,332 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 31)
Exomes 𝑓: 0.0018 ( 6 hom. )

Consequence

STXBP5
ENST00000546097.5 missense

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.16
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]
STXBP5-AS1 (HGNC:44183): (STXBP5 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 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=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-147204527-G-A is Benign according to our data. Variant chr6-147204527-G-A is described in ClinVar as [Benign]. Clinvar id is 3033968.Status of the report is criteria_provided_single_submitter, 1 stars.
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 265 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
STXBP5NM_001127715.4 linkuse as main transcriptc.-6G>A 5_prime_UTR_variant 1/28 ENST00000321680.11
STXBP5-AS1NR_034115.1 linkuse as main transcriptn.88C>T non_coding_transcript_exon_variant 1/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
STXBP5ENST00000321680.11 linkuse as main transcriptc.-6G>A 5_prime_UTR_variant 1/285 NM_001127715.4 A1Q5T5C0-1
STXBP5-AS1ENST00000660355.1 linkuse as main transcriptn.29C>T non_coding_transcript_exon_variant 1/12

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00174
AC:
265
AN:
152028
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00543
Gnomad SAS
AF:
0.000416
Gnomad FIN
AF:
0.0101
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00157
Gnomad OTH
AF:
0.00192
GnomAD3 exomes
AF:
0.00231
AC:
565
AN:
244892
Hom.:
4
AF XY:
0.00211
AC XY:
282
AN XY:
133664
show subpopulations
Gnomad AFR exome
AF:
0.000197
Gnomad AMR exome
AF:
0.000204
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00351
Gnomad SAS exome
AF:
0.00128
Gnomad FIN exome
AF:
0.0113
Gnomad NFE exome
AF:
0.00179
Gnomad OTH exome
AF:
0.00268
GnomAD4 exome
AF:
0.00179
AC:
2616
AN:
1459186
Hom.:
6
Cov.:
31
AF XY:
0.00181
AC XY:
1311
AN XY:
725908
show subpopulations
Gnomad4 AFR exome
AF:
0.0000900
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.0000384
Gnomad4 EAS exome
AF:
0.00332
Gnomad4 SAS exome
AF:
0.00140
Gnomad4 FIN exome
AF:
0.0105
Gnomad4 NFE exome
AF:
0.00151
Gnomad4 OTH exome
AF:
0.00176
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00174
AC:
265
AN:
152146
Hom.:
1
Cov.:
31
AF XY:
0.00220
AC XY:
164
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.000337
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00544
Gnomad4 SAS
AF:
0.000416
Gnomad4 FIN
AF:
0.0101
Gnomad4 NFE
AF:
0.00157
Gnomad4 OTH
AF:
0.00190
Alfa
AF:
0.00159
Hom.:
1
Bravo
AF:
0.00102
Asia WGS
AF:
0.00520
AC:
18
AN:
3478
EpiCase
AF:
0.00109
EpiControl
AF:
0.00173

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

STXBP5-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJan 25, 2023This variant is classified as 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
-0.38
Cadd
Benign
20
Dann
Benign
0.96

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: rs3811106; hg19: chr6-147525663; COSMIC: COSV51652629; COSMIC: COSV51652629; API