Variant 6-147315617-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001127715.4(STXBP5):c.1505A>G(p.Tyr502Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00458 in 1,613,960 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 17 hom. )

Consequence

STXBP5
NM_001127715.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.46

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009953707).

BP6

Variant 6-147315617-A-G is Benign according to our data. Variant chr6-147315617-A-G is described in ClinVar as [Benign]. Clinvar id is 779426.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 560 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP5	NM_001127715.4 linkuse as main transcript	c.1505A>G	p.Tyr502Cys	missense_variant	15/28	ENST00000321680.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP5	ENST00000321680.11 linkuse as main transcript	c.1505A>G	p.Tyr502Cys	missense_variant	15/28	5	NM_001127715.4	A1	Q5T5C0-1

Frequencies

GnomAD3 genomes

AF:

0.00368

AC:

560

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0114

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00525

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00395

AC:

991

AN:

251122

Hom.:

AF XY:

0.00411

AC XY:

558

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00824

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.0110

Gnomad NFE exome

AF:

0.00508

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00468

AC:

6837

AN:

1461632

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

3350

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.00827

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.0120

Gnomad4 NFE exome

AF:

0.00509

Gnomad4 OTH exome

AF:

0.00330

GnomAD4 genome

AF:

0.00368

AC:

560

AN:

152328

Hom.:

Cov.:

AF XY:

0.00375

AC XY:

279

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000649

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0114

Gnomad4 NFE

AF:

0.00525

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00501

Hom.:

Bravo

AF:

0.00271

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00581

AC:

ExAC

AF:

0.00364

AC:

442

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 17, 2018

- -

STXBP5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 04, 2021

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

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.54

.;D;.

Eigen

Benign

0.070

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

D;D;D

MetaRNN

Benign

0.010

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-4.1

D;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0040

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

0.90

P;P;.

Vest4

0.56

MVP

0.068

MPC

0.63

ClinPred

0.075

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.89

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