chr13-42964136-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_033255.5(EPSTI1):c.335G>A(p.Gly112Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000066 in 151,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
EPSTI1
NM_033255.5 missense
NM_033255.5 missense
Scores
5
7
6
Clinical Significance
Conservation
PhyloP100: 4.29
Genes affected
EPSTI1 (HGNC:16465): (epithelial stromal interaction 1) The protein encoded by this gene has been shown to promote tumor invasion and metastasis in some invasive cancer cells when overexpressed. Expression of this gene has been shown to be upregulated by direct binding of the Kruppel like factor 8 protein to promoter sequences. The translated protein interacts with the amino terminal region of the valosin containing protein gene product, resulting in the nuclear translocation of the nuclear factor kappa B subunit 1 gene product, and activation of target genes. Overexpression of this gene has been observed in some breast cancers and in some individuals with systemic lupus erythematosus (SLE). [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.783
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPSTI1 | NM_033255.5 | c.335G>A | p.Gly112Glu | missense_variant | 4/11 | ENST00000313624.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPSTI1 | ENST00000313624.12 | c.335G>A | p.Gly112Glu | missense_variant | 4/11 | 1 | NM_033255.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000660 AC: 1AN: 151584Hom.: 0 Cov.: 32
GnomAD3 genomes
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32
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GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? AF: 0.00000660 AC: 1AN: 151584Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74046
GnomAD4 genome
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74046
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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 | May 27, 2022 | The c.335G>A (p.G112E) alteration is located in exon 4 (coding exon 4) of the EPSTI1 gene. This alteration results from a G to A substitution at nucleotide position 335, causing the glycine (G) at amino acid position 112 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
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D
REVEL
Benign
Sift
Pathogenic
D;D;D
Sift4G
Benign
T;T;T
Polyphen
D;D;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0483);Loss of MoRF binding (P = 0.0483);Loss of MoRF binding (P = 0.0483);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at