12-132673577-G-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting
The NM_006231.4(POLE):āc.1357C>Gā(p.Gln453Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000416 in 1,611,728 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006231.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000361 AC: 9AN: 249146Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134880
GnomAD4 exome AF: 0.0000411 AC: 60AN: 1459524Hom.: 0 Cov.: 34 AF XY: 0.0000468 AC XY: 34AN XY: 726158
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74350
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25032700, 29056344, 20951805) -
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Hereditary cancer-predisposing syndrome Uncertain:2
The p.Q453E variant (also known as c.1357C>G), located in coding exon 13 of the POLE gene, results from a C to G substitution at nucleotide position 1357. The glutamine at codon 453 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
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not specified Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at