Variant rs17740066 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001308330.2(STXBP5L):c.2491G>A(p.Val831Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 1,605,206 control chromosomes in the GnomAD database, including 8,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.079 ( 601 hom., cov: 32)

Exomes 𝑓: 0.099 ( 7832 hom. )

Consequence

STXBP5L
NM_001308330.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.95

Variant links:

Genes affected

STXBP5L (HGNC:30757): (syntaxin binding protein 5L) The protein encoded by this gene is similar to syntaxin-binding protein 5 and contains ten N-terminal WD40 repeats, four variable region WD40 repeats, and a C-terminal R-SNARE domain. Studies of the orthologous proteins in mouse and rat have shown that the encoded protein may inhibit exocytosis in neurosecretory cells, and may negatively regulate the secretion of insulin. A missense variant in this gene is likely the cause of an infantile-onset neurodegenerative disorder diagnosed in two siblings of consanguineous parents. [provided by RefSeq, Jan 2017]

STXBP5L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033420622).

BP6

Variant 3-121381436-G-A is Benign according to our data. Variant chr3-121381436-G-A is described in ClinVar as [Benign]. Clinvar id is 3056299.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-121381436-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP5L	NM_001308330.2 linkuse as main transcript	c.2491G>A	p.Val831Ile	missense_variant	22/27	ENST00000471454.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP5L	ENST00000471454.6 linkuse as main transcript	c.2491G>A	p.Val831Ile	missense_variant	22/27	2	NM_001308330.2	A1

Frequencies

GnomAD3 genomes

AF:

0.0793

AC:

12043

AN:

151816

Hom.:

600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0199

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.0982

Gnomad EAS

AF:

0.0551

Gnomad SAS

AF:

0.0578

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.0878

GnomAD3 exomes

AF:

0.0973

AC:

23355

AN:

240050

Hom.:

1442

AF XY:

0.0934

AC XY:

12192

AN XY:

130474

show subpopulations

Gnomad AFR exome

AF:

0.0192

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.0511

Gnomad SAS exome

AF:

0.0491

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.0991

AC:

143966

AN:

1453272

Hom.:

7832

Cov.:

AF XY:

0.0970

AC XY:

70149

AN XY:

723000

show subpopulations

Gnomad4 AFR exome

AF:

0.0147

Gnomad4 AMR exome

AF:

0.167

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.0351

Gnomad4 SAS exome

AF:

0.0511

Gnomad4 FIN exome

AF:

0.122

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.0952

GnomAD4 genome

AF:

0.0793

AC:

12047

AN:

151934

Hom.:

601

Cov.:

AF XY:

0.0789

AC XY:

5853

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.0198

Gnomad4 AMR

AF:

0.120

Gnomad4 ASJ

AF:

0.0982

Gnomad4 EAS

AF:

0.0554

Gnomad4 SAS

AF:

0.0587

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.0878

Alfa

AF:

0.0962

Hom.:

1928

Bravo

AF:

0.0788

TwinsUK

AF:

0.0982

AC:

364

ALSPAC

AF:

0.102

AC:

393

ESP6500AA

AF:

0.0208

AC:

ESP6500EA

AF:

0.108

AC:

890

ExAC

AF:

0.0928

AC:

11216

Asia WGS

AF:

0.0830

AC:

290

AN:

3478

EpiCase

AF:

0.0958

EpiControl

AF:

0.0969

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

STXBP5L-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 10, 2019

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

0.10

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

T;T;T;T;.;T

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D;D;D;D;D

MetaRNN

Benign

0.0033

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;.;.;.;.

MutationTaster

Benign

0.0000036

P;P;P;P;P

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.52

N;N;N;N;N;N

REVEL

Benign

0.097

Sift

Benign

0.33

T;T;T;T;T;T

Sift4G

Benign

0.50

T;T;T;T;T;T

Polyphen

1.0

D;D;.;.;.;.

Vest4

0.45

MPC

0.38

ClinPred

0.015

GERP RS

5.1

Varity_R

0.081

gMVP

0.36

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