3-121205946-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001308330.2(STXBP5L):c.901A>G(p.Lys301Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
STXBP5L
NM_001308330.2 missense
NM_001308330.2 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 7.09
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STXBP5L | NM_001308330.2 | c.901A>G | p.Lys301Glu | missense_variant | 10/27 | ENST00000471454.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STXBP5L | ENST00000471454.6 | c.901A>G | p.Lys301Glu | missense_variant | 10/27 | 2 | NM_001308330.2 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000533 AC: 1AN: 187718Hom.: 0 AF XY: 0.00000964 AC XY: 1AN XY: 103696
GnomAD3 exomes
AF:
AC:
1
AN:
187718
Hom.:
AF XY:
AC XY:
1
AN XY:
103696
Gnomad AFR exome
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GnomAD4 exome Cov.: 27
GnomAD4 exome
Cov.:
27
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ExAC
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 13, 2024 | The c.901A>G (p.K301E) alteration is located in exon 10 (coding exon 9) of the STXBP5L gene. This alteration results from a A to G substitution at nucleotide position 901, causing the lysine (K) at amino acid position 301 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
D;D;.;.;.;.
Vest4
MutPred
Gain of ubiquitination at K306 (P = 0.0185);Gain of ubiquitination at K306 (P = 0.0185);Gain of ubiquitination at K306 (P = 0.0185);Gain of ubiquitination at K306 (P = 0.0185);Gain of ubiquitination at K306 (P = 0.0185);Gain of ubiquitination at K306 (P = 0.0185);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at