rs769630098
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM4_Supporting
The NM_006231.4(POLE):βc.5672_5674delβ(p.Thr1891del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,494 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: not found (cov: 32)
Exomes π: 0.0000041 ( 0 hom. )
Consequence
POLE
NM_006231.4 inframe_deletion
NM_006231.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.58
Genes affected
POLE (HGNC:9177): (DNA polymerase epsilon, catalytic subunit) This gene encodes the catalytic subunit of DNA polymerase epsilon. The enzyme is involved in DNA repair and chromosomal DNA replication. Mutations in this gene have been associated with colorectal cancer 12 and facial dysmorphism, immunodeficiency, livedo, and short stature. [provided by RefSeq, Sep 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_006231.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.5672_5674del | p.Thr1891del | inframe_deletion | 41/49 | ENST00000320574.10 | |
POLE | XM_011534795.4 | c.5672_5674del | p.Thr1891del | inframe_deletion | 41/48 | ||
POLE | XM_011534797.4 | c.4751_4753del | p.Thr1584del | inframe_deletion | 33/40 | ||
POLE | XM_011534802.4 | c.2660_2662del | p.Thr887del | inframe_deletion | 17/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.5672_5674del | p.Thr1891del | inframe_deletion | 41/49 | 1 | NM_006231.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251140Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135690
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461494Hom.: 0 AF XY: 0.00000550 AC XY: 4AN XY: 727034
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 484509). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is present in population databases (rs769630098, gnomAD 0.02%). This variant, c.5672_5674del, results in the deletion of 1 amino acid(s) of the POLE protein (p.Thr1891del), but otherwise preserves the integrity of the reading frame. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 30, 2019 | The c.5672_5674delCCA variant (also known as p.T1891del) is located in coding exon 41 of the POLE gene. This variant results from an in-frame deletion of 3 nucleotides at positions 5672 to 5674 and causes the removal of a well-conserved threonine residue at codon 1891. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
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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