rs3811106

Variant names:

• chr6-147204527-G-A
• rs3811106
• ENST00000546097.5:c.103G>A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The ENST00000546097.5(STXBP5):​c.103G>A​(p.Glu35Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00179 in 1,611,332 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0018 (6 hom.)
• Consequence: STXBP5 ENST00000546097.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.16

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]

STXBP5-AS1 (HGNC:44183): (STXBP5 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 6-147204527-G-A is Benign according to our data. Variant chr6-147204527-G-A is described in ClinVar as [Benign]. Clinvar id is 3033968.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 265 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP5	NM_001127715.4	c.-6G>A		5_prime_UTR_variant	Exon 1 of 28	ENST00000321680.11	NP_001121187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP5	ENST00000321680	c.-6G>A		5_prime_UTR_variant	Exon 1 of 28	5	NM_001127715.4	ENSP00000321826.6

Frequencies

GnomAD3 genomes AF: 0.00174 AC: 265 AN: 152028 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00543

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00231 AC: 565 AN: 244892 Hom.: 4 AF XY: 0.00211 AC XY: 282 AN XY: 133664

Gnomad AFR exome AF: 0.000197

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00351

Gnomad SAS exome AF: 0.00128

Gnomad FIN exome AF: 0.0113

Gnomad NFE exome AF: 0.00179

Gnomad OTH exome AF: 0.00268

GnomAD4 exome AF: 0.00179 AC: 2616 AN: 1459186 Hom.: 6 Cov.: 31 AF XY: 0.00181 AC XY: 1311 AN XY: 725908

Gnomad4 AFR exome AF: 0.0000900

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00332

Gnomad4 SAS exome AF: 0.00140

Gnomad4 FIN exome AF: 0.0105

Gnomad4 NFE exome AF: 0.00151

Gnomad4 OTH exome AF: 0.00176

GnomAD4 genome AF: 0.00174 AC: 265 AN: 152146 Hom.: 1 Cov.: 31 AF XY: 0.00220 AC XY: 164 AN XY: 74380

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00544

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.0101

Gnomad4 NFE AF: 0.00157

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00159 Hom.: 1

Bravo AF: 0.00102

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.00173

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

STXBP5-related disorder Benign:1

Jan 25, 2023

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.96

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

Publications

LitVar

Other links and lift over

dbSNP: rs3811106; hg19: chr6-147525663; COSMIC: COSV51652629; COSMIC: COSV51652629;