9-127612418-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_003165.6(STXBP1):​c.15C>T​(p.Gly5Gly) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G5G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

STXBP1
NM_003165.6 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

0 publications found
Variant links:
Genes affected
STXBP1 (HGNC:11444): (syntaxin binding protein 1) This gene encodes a syntaxin-binding protein. The encoded protein appears to play a role in release of neurotransmitters via regulation of syntaxin, a transmembrane attachment protein receptor. Mutations in this gene have been associated with infantile epileptic encephalopathy-4. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]
STXBP1 Gene-Disease associations (from GenCC):
  • developmental and epileptic encephalopathy, 4
    Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • genetic developmental and epileptic encephalopathy
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
  • atypical Rett syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • autosomal dominant non-syndromic intellectual disability
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Dravet syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • infantile spasms
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • undetermined early-onset epileptic encephalopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • autism spectrum disorder
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
  • intellectual disability
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP7
Synonymous conserved (PhyloP=-1.07 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STXBP1NM_003165.6 linkc.15C>T p.Gly5Gly synonymous_variant Exon 1 of 20 ENST00000373302.8 NP_003156.1 P61764-2
STXBP1NM_001032221.6 linkc.15C>T p.Gly5Gly synonymous_variant Exon 1 of 19 ENST00000373299.5 NP_001027392.1 P61764-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STXBP1ENST00000373302.8 linkc.15C>T p.Gly5Gly synonymous_variant Exon 1 of 20 1 NM_003165.6 ENSP00000362399.3 P61764-2
STXBP1ENST00000373299.5 linkc.15C>T p.Gly5Gly synonymous_variant Exon 1 of 19 1 NM_001032221.6 ENSP00000362396.2 P61764-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1445712
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
719094
African (AFR)
AF:
0.00
AC:
0
AN:
31658
American (AMR)
AF:
0.00
AC:
0
AN:
43608
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25602
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38454
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84450
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51754
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5718
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1104940
Other (OTH)
AF:
0.00
AC:
0
AN:
59528
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
CADD
Benign
13
DANN
Benign
0.96
PhyloP100
-1.1
PromoterAI
-0.090
Neutral

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

Other links and lift over

dbSNP: rs2132275559; hg19: chr9-130374697; API