Variant 17-54990825-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178509.6(STXBP4):c.48G>T(p.Lys16Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

STXBP4
NM_178509.6 missense, splice_region

Scores

Splicing: ADA: 0.9949

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0540

Variant links:

Genes affected

STXBP4 (HGNC:19694): (syntaxin binding protein 4) Enables syntaxin binding activity. Involved in several processes, including positive regulation of cell cycle G1/S phase transition; positive regulation of keratinocyte proliferation; and protein stabilization. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

STXBP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP4	NM_178509.6 linkuse as main transcript	c.48G>T	p.Lys16Asn	missense_variant, splice_region_variant	4/18	ENST00000376352.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP4	ENST00000376352.6 linkuse as main transcript	c.48G>T	p.Lys16Asn	missense_variant, splice_region_variant	4/18	2	NM_178509.6	P1	Q6ZWJ1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445964

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719060

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 22, 2023

The c.48G>T (p.K16N) alteration is located in exon 4 (coding exon 2) of the STXBP4 gene. This alteration results from a G to T substitution at nucleotide position 48, causing the lysine (K) at amino acid position 16 to be replaced by an asparagine (N). 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

Benign

0.18

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0072

T;T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.4

M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.51

N;N;N

REVEL

Benign

0.027

Sift

Uncertain

0.024

D;D;D

Sift4G

Benign

0.30

T;T;T

Polyphen

0.36

B;.;P

Vest4

0.20

MutPred

0.46

Loss of ubiquitination at K16 (P = 0.0071);Loss of ubiquitination at K16 (P = 0.0071);Loss of ubiquitination at K16 (P = 0.0071);

MVP

0.41

MPC

0.18

ClinPred

0.32

GERP RS

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.058

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.74

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: 16

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