NM_006873.4:c.353G>A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006873.4(STON1):c.353G>A(p.Gly118Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,423,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G118V) has been classified as Benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
STON1
NM_006873.4 missense
NM_006873.4 missense
Scores
3
16
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.279
Genes affected
STON1 (HGNC:17003): (stonin 1) Endocytosis of cell surface proteins is mediated by a complex molecular machinery that assembles on the inner surface of the plasma membrane. This gene encodes one of two human homologs of the Drosophila melanogaster stoned B protein. This protein is related to components of the endocytic machinery and exhibits a modular structure consisting of an N-terminal proline-rich domain, a central region of homology specific to the human stoned B-like proteins, and a C-terminal region homologous to the mu subunits of adaptor protein (AP) complexes. Read-through transcription of this gene into the neighboring downstream gene, which encodes TFIIA-alpha/beta-like factor, generates a transcript (SALF), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]
STON1-GTF2A1L (HGNC:30651): (STON1-GTF2A1L readthrough) STON1-GTF2A1L mRNAs are infrequent but naturally occurring read-through products of the neighboring STON1 and GTF2A1L genes. These transcripts encode fusion proteins composed of the vast majority of each of the individual elements, stonin 1 and general transcription factor IIA, 1-like. Alternative splicing results in multiple transcript variants. The significance of these read-through variants and the function of the resulting protein products have not yet been determined. [provided by RefSeq, Oct 2010]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1060707).
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| STON1 | ENST00000404752.6 | c.353G>A | p.Gly118Glu | missense_variant | Exon 2 of 4 | 1 | NM_006873.4 | ENSP00000385273.1 | ||
| STON1-GTF2A1L | ENST00000394754.5 | c.353G>A | p.Gly118Glu | missense_variant | Exon 2 of 11 | 1 | ENSP00000378236.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 7.02e-7 AC: 1AN: 1423622Hom.: 0 Cov.: 36 AF XY: 0.00000142 AC XY: 1AN XY: 705112 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1423622
Hom.:
Cov.:
36
AF XY:
AC XY:
1
AN XY:
705112
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32240
American (AMR)
AF:
AC:
0
AN:
38174
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
23370
East Asian (EAS)
AF:
AC:
0
AN:
39360
South Asian (SAS)
AF:
AC:
0
AN:
77982
European-Finnish (FIN)
AF:
AC:
0
AN:
52000
Middle Eastern (MID)
AF:
AC:
0
AN:
5580
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1096142
Other (OTH)
AF:
AC:
0
AN:
58774
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;.;T;.;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.;.;.;.
PhyloP100
PrimateAI
Benign
T
PROVEAN
Benign
.;N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
.;D;D;D;D;D;D
Sift4G
Uncertain
.;D;D;D;D;D;D
Polyphen
B;B;B;B;.;B;.
Vest4
0.16, 0.19, 0.14, 0.20, 0.19
MutPred
Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);
MVP
0.28
MPC
0.0032
ClinPred
T
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
Publications
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