16-31034089-G-T

Position:

• chr16-31034089-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_004604.5(STX4):​c.107G>T​(p.Ser36Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 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)
• Consequence: STX4 NM_004604.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.201

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity STX4_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.116138786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX4	NM_004604.5	c.107G>T	p.Ser36Ile	missense_variant	2/11	ENST00000313843.8	NP_004595.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX4	ENST00000313843.8	c.107G>T	p.Ser36Ile	missense_variant	2/11	1	NM_004604.5	ENSP00000317714.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.107G>T (p.S36I) alteration is located in exon 2 (coding exon 2) of the STX4 gene. This alteration results from a G to T substitution at nucleotide position 107, causing the serine (S) at amino acid position 36 to be replaced by an isoleucine (I). 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	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Benign	0.96
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.054
Sift	Pathogenic	0.0	D
Vest4		0.27
MutPred		0.31		Gain of glycosylation at A27 (P = 0.0019);
MVP		0.24
ClinPred		0.92	D
GERP RS		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-31045410;