6-147314277-A-T

Position:

• chr6-147314277-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001127715.4(STXBP5):​c.1307A>T​(p.Asn436Ile) variant causes a missense 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N436S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: STXBP5 NM_001127715.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93

Genes affected

STXBP5 (HGNC:19665): (syntaxin binding protein 5) Syntaxin 1 is a component of the 7S and 20S SNARE complexes which are involved in docking and fusion of synaptic vesicles with the presynaptic plasma membrane. This gene encodes a syntaxin 1 binding protein. In rat, a similar protein dissociates syntaxin 1 from the Munc18/n-Sec1/rbSec1 complex to form a 10S complex, an intermediate which can be converted to the 7S SNARE complex. Thus this protein is thought to be involved in neurotransmitter release by stimulating SNARE complex formation. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24121779).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP5	NM_001127715.4	c.1307A>T	p.Asn436Ile	missense_variant	13/28	ENST00000321680.11	NP_001121187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP5	ENST00000321680.11	c.1307A>T	p.Asn436Ile	missense_variant	13/28	5	NM_001127715.4	ENSP00000321826	A1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.54	.;D;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.048
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.83	L;L;L
MutationTaster	Benign	0.38	P;P;P;P
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Benign	0.083
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.045	B;B;.
Vest4		0.45
MutPred		0.45		Loss of disorder (P = 0.0485);Loss of disorder (P = 0.0485);Loss of disorder (P = 0.0485);
MVP		0.093
MPC		0.63
ClinPred		0.97	D
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.77

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: rs1039084; hg19: chr6-147635413;