NM_178509.6:c.288-7G>C

Variant names:

• chr17-54999625-G-C
• rs11658717
• NM_178509.6:c.288-7G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178509.6(STXBP4):​c.288-7G>C variant causes a splice region, intron 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. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STXBP4 NM_178509.6 splice_region, intron
• Scores: Splicing: ADA: 0.00003773
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 29 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.407638).

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.288-7G>C		splice_region intron	N/A	NP_848604.3
	STXBP4	NM_001398481.1		c.288-1G>C		splice_acceptor intron	N/A	NP_001385410.1
	STXBP4	NM_001398483.1		c.288-7G>C		splice_region intron	N/A	NP_001385412.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP4	ENST00000376352.6	TSL:2 MANE Select	c.288-7G>C		splice_region intron	N/A	ENSP00000365530.2
	STXBP4	ENST00000434978.6	TSL:1	c.288-7G>C		splice_region intron	N/A	ENSP00000391087.2
	STXBP4	ENST00000398391.6	TSL:1	c.57-1G>C		splice_acceptor intron	N/A	ENSP00000381427.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.83
DANN	Benign	0.71
Eigen	Benign	0.11
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.078	N
PhyloP100		1.2
GERP RS		2.4
PromoterAI		-0.0049	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000038
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

Other links and lift over

dbSNP: rs11658717; hg19: chr17-53076986;