Variant 16-31038642-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004604.5(STX4):c.697A>C(p.Met233Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,748 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: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

STX4
NM_004604.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.768

Variant links:

Genes affected

STX4 (HGNC:11439): (syntaxin 4) Enables sphingomyelin phosphodiesterase activator activity. Involved in several processes, including cornified envelope assembly; positive regulation of immune effector process; and positive regulation of protein localization. Located in several cellular components, including basolateral plasma membrane; cytoplasmic vesicle; and lamellipodium. Part of SNARE complex. Is active in glutamatergic synapse and postsynapse. [provided by Alliance of Genome Resources, Apr 2022]

STX4 links:

STX4 (HGNC:):

STX4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09989673).

BS2

High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX4	NM_004604.5 linkuse as main transcript	c.697A>C	p.Met233Leu	missense_variant	8/11	ENST00000313843.8	NP_004595.2	Q12846-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX4	ENST00000313843.8 linkuse as main transcript	c.697A>C	p.Met233Leu	missense_variant	8/11	1	NM_004604.5	ENSP00000317714.3		Q12846-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250898

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Alfa

AF:

0.000144

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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 08, 2021

The c.697A>C (p.M233L) alteration is located in exon 8 (coding exon 8) of the STX4 gene. This alteration results from a A to C substitution at nucleotide position 697, causing the methionine (M) at amino acid position 233 to be replaced by a leucine (L). 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

0.16

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.17

.;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

.;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.69

N;N

REVEL

Benign

0.063

Sift

Benign

0.14

T;T

Sift4G

Benign

0.066

.;T

Polyphen

0.0020

.;B

Vest4

0.27

MutPred

0.35

.;Gain of relative solvent accessibility (P = 0.2363);

MVP

0.37

MPC

0.56

ClinPred

0.068

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.073

gMVP

0.71

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