rs777503236
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_006231.4(POLE):c.6547C>T(p.Pro2183Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,611,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006231.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.6547C>T | p.Pro2183Ser | missense_variant | Exon 47 of 49 | ENST00000320574.10 | NP_006222.2 | |
POLE | XM_011534795.4 | c.6547C>T | p.Pro2183Ser | missense_variant | Exon 47 of 48 | XP_011533097.1 | ||
POLE | XM_011534797.4 | c.5626C>T | p.Pro1876Ser | missense_variant | Exon 39 of 40 | XP_011533099.1 | ||
POLE | XM_011534802.4 | c.3535C>T | p.Pro1179Ser | missense_variant | Exon 23 of 24 | XP_011533104.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248952Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134752
GnomAD4 exome AF: 0.00000617 AC: 9AN: 1459390Hom.: 0 Cov.: 34 AF XY: 0.00000551 AC XY: 4AN XY: 726104
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
not provided Uncertain:1
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 540701). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is present in population databases (rs777503236, gnomAD 0.01%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2183 of the POLE protein (p.Pro2183Ser). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at