2-48581721-A-C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_006873.4(STON1):c.1088A>C(p.Lys363Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,458,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
STON1
NM_006873.4 missense
NM_006873.4 missense
Scores
5
7
7
Clinical Significance
Conservation
PhyloP100: 7.48
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| STON1 | ENST00000404752.6 | c.1088A>C | p.Lys363Thr | missense_variant | Exon 2 of 4 | 1 | NM_006873.4 | ENSP00000385273.1 | ||
| STON1-GTF2A1L | ENST00000394754.5 | c.1088A>C | p.Lys363Thr | missense_variant | Exon 2 of 11 | 1 | ENSP00000378236.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.0000122 AC: 3AN: 245616 AF XY: 0.0000150 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
245616
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000480 AC: 7AN: 1458842Hom.: 0 Cov.: 103 AF XY: 0.00000551 AC XY: 4AN XY: 725552 show subpopulations
GnomAD4 exome
AF:
AC:
7
AN:
1458842
Hom.:
Cov.:
103
AF XY:
AC XY:
4
AN XY:
725552
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33188
American (AMR)
AF:
AC:
0
AN:
44048
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25972
East Asian (EAS)
AF:
AC:
0
AN:
39690
South Asian (SAS)
AF:
AC:
0
AN:
85396
European-Finnish (FIN)
AF:
AC:
0
AN:
53382
Middle Eastern (MID)
AF:
AC:
0
AN:
5736
European-Non Finnish (NFE)
AF:
AC:
7
AN:
1111214
Other (OTH)
AF:
AC:
0
AN:
60216
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
2
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Mar 22, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.1088A>C (p.K363T) alteration is located in exon 2 (coding exon 1) of the STON1-GTF2A1L gene. This alteration results from a A to C substitution at nucleotide position 1088, causing the lysine (K) at amino acid position 363 to be replaced by a threonine (T). 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
DANN
Uncertain
DEOGEN2
Benign
T;T;T;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;.;D;.;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.;.;.;.
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D;D;D;D;D;D
REVEL
Benign
Sift
Uncertain
.;D;D;D;D;D;D
Sift4G
Pathogenic
.;D;D;D;D;D;D
Polyphen
D;D;D;D;.;D;.
Vest4
0.58, 0.58, 0.54, 0.56, 0.55, 0.56
MutPred
Loss of ubiquitination at K363 (P = 0.013);Loss of ubiquitination at K363 (P = 0.013);Loss of ubiquitination at K363 (P = 0.013);Loss of ubiquitination at K363 (P = 0.013);Loss of ubiquitination at K363 (P = 0.013);Loss of ubiquitination at K363 (P = 0.013);Loss of ubiquitination at K363 (P = 0.013);
MVP
0.53
MPC
0.012
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
Publications
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