17-54990899-G-T

Variant names:

• chr17-54990899-G-T
• rs778811461
• NM_178509.6:c.122G>T

Variant summary

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

The NM_178509.6(STXBP4):​c.122G>T​(p.Arg41Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,451,654 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: STXBP4 NM_178509.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.03

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 rank	MANE	Protein	UniProt
STXBP4	NM_178509.6	c.122G>T	p.Arg41Leu	missense_variant	Exon 4 of 18	ENST00000376352.6	NP_848604.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP4	ENST00000376352.6	c.122G>T	p.Arg41Leu	missense_variant	Exon 4 of 18	2	NM_178509.6	ENSP00000365530.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451654 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722036

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T;T;T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	2.0	M;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.024	D;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.70
MutPred		0.39		Gain of sheet (P = 0.1539);Gain of sheet (P = 0.1539);Gain of sheet (P = 0.1539);
MVP		0.66
MPC		0.71
ClinPred		0.99	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs778811461; hg19: chr17-53068260;