Variant chr6-147204527-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

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 (no stars).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0018 ( 6 hom. )

Consequence

STXBP5
ENST00000546097.5 missense

Scores

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 links:

STXBP5-AS1 (HGNC:44183): (STXBP5 antisense RNA 1)

STXBP5-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

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 no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 265 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP5	NM_001127715.4 linkuse as main transcript	c.-6G>A		5_prime_UTR_variant	1/28	ENST00000321680.11
STXBP5-AS1	NR_034115.1 linkuse as main transcript	n.88C>T		non_coding_transcript_exon_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP5	ENST00000321680.11 linkuse as main transcript	c.-6G>A		5_prime_UTR_variant	1/28	5	NM_001127715.4	A1	Q5T5C0-1
STXBP5-AS1	ENST00000660355.1 linkuse as main transcript	n.29C>T		non_coding_transcript_exon_variant	1/12

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

265

AN:

152028

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00174

AC:

265

AN:

152146

Hom.:

Cov.:

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.:

Bravo

AF:

0.00102

Asia WGS

AF:

0.00520

AC:

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 submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 25, 2023

This 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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over