Variant 17-55081178-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178509.6(STXBP4):c.1484T>C(p.Met495Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000115 in 1,478,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

STXBP4
NM_178509.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

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:

LOC107985002 (HGNC:):

LOC107985002 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04467061).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP4	NM_178509.6 linkuse as main transcript	c.1484T>C	p.Met495Thr	missense_variant	16/18	ENST00000376352.6	NP_848604.3
LOC107985002	XR_001752943.2 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP4	ENST00000376352.6 linkuse as main transcript	c.1484T>C	p.Met495Thr	missense_variant	16/18	2	NM_178509.6	ENSP00000365530	P1	Q6ZWJ1-1
STXBP4	ENST00000434978.6 linkuse as main transcript	c.1418T>C	p.Met473Thr	missense_variant	15/17	1		ENSP00000391087

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000134

AC:

AN:

149712

Hom.:

AF XY:

0.0000241

AC XY:

AN XY:

83012

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000118

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000131

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000830

AC:

AN:

1325910

Hom.:

Cov.:

AF XY:

0.0000107

AC XY:

AN XY:

655152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000618

Gnomad4 SAS exome

AF:

0.0000301

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000572

Gnomad4 OTH exome

AF:

0.0000185

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000113

ExAC

AF:

0.00000826

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

Mar 14, 2023

The c.1484T>C (p.M495T) alteration is located in exon 16 (coding exon 14) of the STXBP4 gene. This alteration results from a T to C substitution at nucleotide position 1484, causing the methionine (M) at amino acid position 495 to be replaced by a threonine (T). 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

0.078

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.37

DEOGEN2

Benign

0.0083

T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

0.88

N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.62

N;N

REVEL

Benign

0.029

Sift

Benign

0.28

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.022

B;B

Vest4

0.10

MutPred

0.47

Loss of stability (P = 0.0023);.;

MVP

0.46

MPC

0.17

ClinPred

0.031

GERP RS

3.2

Varity_R

0.051

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