17-55031239-C-G

Variant names:

• chr17-55031239-C-G
• NM_178509.6:c.738C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178509.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP4	NM_178509.6	MANE Select	c.738C>G	p.Asp246Glu	missense	Exon 9 of 18	NP_848604.3	Q6ZWJ1-1
	STXBP4	NM_001398481.1		c.744C>G	p.Asp248Glu	missense	Exon 9 of 18	NP_001385410.1
	STXBP4	NM_001398483.1		c.738C>G	p.Asp246Glu	missense	Exon 9 of 17	NP_001385412.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP4	ENST00000376352.6	TSL:2 MANE Select	c.738C>G	p.Asp246Glu	missense	Exon 9 of 18	ENSP00000365530.2	Q6ZWJ1-1
	STXBP4	ENST00000434978.6	TSL:1	c.738C>G	p.Asp246Glu	missense	Exon 9 of 17	ENSP00000391087.2	E7EPP7
	STXBP4	ENST00000398391.6	TSL:1	c.513C>G	p.Asp171Glu	missense	Exon 8 of 11	ENSP00000381427.2	Q6ZWJ1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		0.24
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.22
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.37		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

Other links and lift over

hg19: chr17-53108600;