3-120909640-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001308330.2(STXBP5L):​c.62G>A​(p.Gly21Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

STXBP5L
NM_001308330.2 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.68
Variant links:
Genes affected
STXBP5L (HGNC:30757): (syntaxin binding protein 5L) The protein encoded by this gene is similar to syntaxin-binding protein 5 and contains ten N-terminal WD40 repeats, four variable region WD40 repeats, and a C-terminal R-SNARE domain. Studies of the orthologous proteins in mouse and rat have shown that the encoded protein may inhibit exocytosis in neurosecretory cells, and may negatively regulate the secretion of insulin. A missense variant in this gene is likely the cause of an infantile-onset neurodegenerative disorder diagnosed in two siblings of consanguineous parents. [provided by RefSeq, Jan 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.17702702).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
STXBP5LNM_001308330.2 linkc.62G>A p.Gly21Asp missense_variant 2/27 ENST00000471454.6 NP_001295259.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STXBP5LENST00000471454.6 linkc.62G>A p.Gly21Asp missense_variant 2/272 NM_001308330.2 ENSP00000420019.1 E9PFI2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1461228
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726902
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

STXBP5L-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesApr 10, 2023The STXBP5L c.62G>A variant is predicted to result in the amino acid substitution p.Gly21Asp. This variant was reported as a de novo finding in an individual with autism spectrum disorder; however, no additional studies have been done to confirm its pathogenicity (Jiang et al. 2013. PubMed ID: 23849776; Yuen et al. 2016. PubMed ID: 27525107). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0097
T;T;T;T;.;.;T
Eigen
Benign
0.11
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.87
D;D;D;D;D;D;D
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.18
T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N;.;.;.;.;.;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-1.4
N;N;N;N;N;N;N
REVEL
Benign
0.042
Sift
Uncertain
0.020
D;D;D;D;D;T;D
Sift4G
Uncertain
0.048
D;D;D;D;D;T;D
Polyphen
0.24
B;B;.;.;.;.;.
Vest4
0.45
MutPred
0.18
Loss of glycosylation at S20 (P = 0.0391);Loss of glycosylation at S20 (P = 0.0391);Loss of glycosylation at S20 (P = 0.0391);Loss of glycosylation at S20 (P = 0.0391);Loss of glycosylation at S20 (P = 0.0391);Loss of glycosylation at S20 (P = 0.0391);Loss of glycosylation at S20 (P = 0.0391);
MVP
0.12
MPC
0.30
ClinPred
0.82
D
GERP RS
5.3
Varity_R
0.21
gMVP
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-120628487; API