Genetic Variant STXBP6:p.Gln24Glu (chr14-24974749-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001394410.1(STXBP6):c.70C>G(p.Gln24Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,450,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

STXBP6
NM_001394410.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3043436).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394410.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STXBP6	NM_001394410.1	MANE Select	c.70C>G	p.Gln24Glu	missense	Exon 2 of 6	NP_001381339.1	Q8NFX7-1
STXBP6	NM_001304476.3		c.70C>G	p.Gln24Glu	missense	Exon 3 of 7	NP_001291405.1	Q8NFX7-1
STXBP6	NM_001304477.3		c.70C>G	p.Gln24Glu	missense	Exon 2 of 6	NP_001291406.1	Q8NFX7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STXBP6	ENST00000323944.10	TSL:1 MANE Select	c.70C>G	p.Gln24Glu	missense	Exon 2 of 6	ENSP00000324302.5	Q8NFX7-1
STXBP6	ENST00000396700.5	TSL:1	c.70C>G	p.Gln24Glu	missense	Exon 3 of 7	ENSP00000379928.1	Q8NFX7-1
STXBP6	ENST00000419632.6	TSL:1	c.70C>G	p.Gln24Glu	missense	Exon 2 of 6	ENSP00000397212.2	Q8NFX7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

234846

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000276

AC:

AN:

1450054

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719932

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33388

American (AMR)

AF:

0.00

AC:

AN:

43768

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25750

East Asian (EAS)

AF:

0.00

AC:

AN:

39586

South Asian (SAS)

AF:

0.00

AC:

AN:

83962

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52796

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000362

AC:

AN:

1105120

Other (OTH)

AF:

0.00

AC:

AN:

59926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.083

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.023

Eigen

Benign

-0.050

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0044

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.16

REVEL

Benign

0.28

Sift

Benign

0.83

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.66

MutPred

0.31

Loss of MoRF binding (P = 0.0516)

MVP

0.12

MPC

0.22

ClinPred

0.77

GERP RS

5.8

Varity_R

0.13

gMVP

0.42

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over