Genetic Variant STXBP6:p.Gly70Ala (chr14-24857103-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001394410.1(STXBP6):c.209G>C(p.Gly70Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,036 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

STXBP6
NM_001394410.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.83

Variant links:

Genes affected

STXBP6 (HGNC:19666): (syntaxin binding protein 6) Enables cadherin binding activity involved in cell-cell adhesion. Predicted to be involved in Golgi to plasma membrane transport and exocytosis. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

STXBP6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25973335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP6	NM_001394410.1 link	c.209G>C	p.Gly70Ala	missense_variant	Exon 3 of 6	ENST00000323944.10	NP_001381339.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP6	ENST00000323944.10 link	c.209G>C	p.Gly70Ala	missense_variant	Exon 3 of 6	1	NM_001394410.1	ENSP00000324302.5		Q8NFX7-1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

251076

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1460894

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726784

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000995

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.209G>C (p.G70A) alteration is located in exon 3 (coding exon 2) of the STXBP6 gene. This alteration results from a G to C substitution at nucleotide position 209, causing the glycine (G) at amino acid position 70 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

0.0056

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.061

T;T;T;T;T

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

.;.;.;.;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.26

T;T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.1

M;M;M;M;M

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.98

N;N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.64

T;T;T;T;T

Sift4G

Uncertain

0.018

D;D;D;D;D

Polyphen

0.97

D;D;D;D;D

Vest4

0.81

MutPred

0.20

Loss of disorder (P = 0.1152);Loss of disorder (P = 0.1152);Loss of disorder (P = 0.1152);Loss of disorder (P = 0.1152);Loss of disorder (P = 0.1152);

MVP

0.33

MPC

0.51

ClinPred

0.38

GERP RS

5.8

Varity_R

0.21

gMVP

0.37

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