6-147382163-A-T

Variant names:

• chr6-147382163-A-T
• rs9399599
• NM_001127715.4:c.3194-615A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127715.4(STXBP5):​c.3194-615A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,964 control chromosomes in the GnomAD database, including 19,946 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (19946 hom., cov: 32)
• Consequence: STXBP5 NM_001127715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127715.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP5	NM_001127715.4	MANE Select	c.3194-615A>T		intron	N/A	NP_001121187.1
	STXBP5	NM_001394409.1		c.3146-615A>T		intron	N/A	NP_001381338.1
	STXBP5	NM_139244.6		c.3086-615A>T		intron	N/A	NP_640337.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP5	ENST00000321680.11	TSL:5 MANE Select	c.3194-615A>T		intron	N/A	ENSP00000321826.6
	STXBP5	ENST00000367481.7	TSL:1	c.3086-615A>T		intron	N/A	ENSP00000356451.3
	STXBP5	ENST00000443556.2	TSL:1	n.3535-615A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77480 AN: 151848 Hom.: 19934 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.519

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.510 AC: 77531 AN: 151964 Hom.: 19946 Cov.: 32 AF XY: 0.506 AC XY: 37544 AN XY: 74248

African (AFR) AF: 0.517 AC: 21419 AN: 41466

American (AMR) AF: 0.532 AC: 8102 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1825 AN: 3468

East Asian (EAS) AF: 0.272 AC: 1403 AN: 5152

South Asian (SAS) AF: 0.487 AC: 2347 AN: 4820

European-Finnish (FIN) AF: 0.482 AC: 5091 AN: 10554

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35693 AN: 67956

Other (OTH) AF: 0.516 AC: 1088 AN: 2108

Alfa AF: 0.511 Hom.: 2488

Bravo AF: 0.514

Asia WGS AF: 0.415 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.38
PhyloP100		-0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs9399599; hg19: chr6-147703299;