17-55031239-C-G

Variant summary

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

The NM_178509.6(STXBP4):c.738C>G(p.Asp246Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STXBP4 NM_178509.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.241

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]

ACMG classification

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	c.738C>G	p.Asp246Glu	missense_variant	9/18	ENST00000376352.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP4	ENST00000376352.6	c.738C>G	p.Asp246Glu	missense_variant	9/18	2	NM_178509.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Dec 01, 2022

The c.738C>G (p.D246E) alteration is located in exon 9 (coding exon 7) of the STXBP4 gene. This alteration results from a C to G substitution at nucleotide position 738, causing the aspartic acid (D) at amino acid position 246 to be replaced by a glutamic acid (E). 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	Pathogenic	0.66
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.35	T;T;T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.75	T;T;T;T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	3.0	M;.;.;.
MutationTaster	Benign	0.97	N;N;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.8	D;N;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.77
MutPred		0.37		Gain of ubiquitination at K248 (P = 0.1378);Gain of ubiquitination at K248 (P = 0.1378);Gain of ubiquitination at K248 (P = 0.1378);.;
MVP		0.55
MPC		0.63
ClinPred		0.99	D
GERP RS		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.36
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-53108600;