6-147267146-C-T

Variant names:

• chr6-147267146-C-T
• rs139727060
• NM_001127715.4:c.693C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_001127715.4(STXBP5):​c.693C>T​(p.Asp231Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,609,994 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: STXBP5 NM_001127715.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.94
• Publications: 2 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]

ENSG00000293909 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 6-147267146-C-T is Benign according to our data. Variant chr6-147267146-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3042400.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.93 with no splicing effect.
• BS2: High AC in GnomAd4 at 36 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP5	NM_001127715.4	MANE Select	c.693C>T	p.Asp231Asp	synonymous	Exon 7 of 28	NP_001121187.1	Q5T5C0-1
	STXBP5	NM_001394409.1		c.693C>T	p.Asp231Asp	synonymous	Exon 7 of 27	NP_001381338.1	H0Y332
	STXBP5	NM_139244.6		c.693C>T	p.Asp231Asp	synonymous	Exon 7 of 26	NP_640337.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP5	ENST00000321680.11	TSL:5 MANE Select	c.693C>T	p.Asp231Asp	synonymous	Exon 7 of 28	ENSP00000321826.6	Q5T5C0-1
	STXBP5	ENST00000367481.7	TSL:1	c.693C>T	p.Asp231Asp	synonymous	Exon 7 of 26	ENSP00000356451.3	Q5T5C0-2
	STXBP5	ENST00000546097.5	TSL:1	c.801C>T	p.Asp267Asp	synonymous	Exon 7 of 10	ENSP00000441479.2	F6VFW0

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00655

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000407 AC: 101 AN: 248128 AF XY: 0.000424

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000299

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00536

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.000226 AC: 330 AN: 1457784 Hom.: 1 Cov.: 30 AF XY: 0.000234 AC XY: 170 AN XY: 725222

African (AFR) AF: 0.00 AC: 0 AN: 33128

American (AMR) AF: 0.0000228 AC: 1 AN: 43798

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00755 AC: 298 AN: 39492

South Asian (SAS) AF: 0.0000234 AC: 2 AN: 85520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110474

Other (OTH) AF: 0.000482 AC: 29 AN: 60210

GnomAD4 genome AF: 0.000237 AC: 36 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74418

African (AFR) AF: 0.00 AC: 0 AN: 41542

American (AMR) AF: 0.000131 AC: 2 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00656 AC: 34 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.000287

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	STXBP5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.59
PhyloP100		2.9
Mutation Taster		=291/9	polymorphism

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

Other links and lift over

dbSNP: rs139727060; hg19: chr6-147588282; COSMIC: COSV51653994;