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. Variant got -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

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 Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP4	NM_178509.6	c.288-7G>C		splice_region_variant, intron_variant	Intron 5 of 17	ENST00000376352.6	NP_848604.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP4	ENST00000376352.6	c.288-7G>C		splice_region_variant, intron_variant	Intron 5 of 17	2	NM_178509.6	ENSP00000365530.2
STXBP4	ENST00000434978.6	c.288-7G>C		splice_region_variant, intron_variant	Intron 5 of 16	1		ENSP00000391087.2
STXBP4	ENST00000398391.6	c.57-1G>C		splice_acceptor_variant, intron_variant	Intron 4 of 10	1		ENSP00000381427.2
STXBP4	ENST00000405898.5	c.288-7G>C		splice_region_variant, intron_variant	Intron 4 of 10	5		ENSP00000385944.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
GERP RS		2.4

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

Publications

LitVar

Other links and lift over

dbSNP: rs11658717; hg19: chr17-53076986;