12-132649826-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_006231.4(POLE):c.3646G>A(p.Gly1216Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000743 in 1,614,002 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1216D) has been classified 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.3646G>A | p.Gly1216Ser | missense_variant | 30/49 | ENST00000320574.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.3646G>A | p.Gly1216Ser | missense_variant | 30/49 | 1 | NM_006231.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000167 AC: 42AN: 251276Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135874
GnomAD4 exome AF: 0.0000684 AC: 100AN: 1461828Hom.: 0 Cov.: 32 AF XY: 0.0000660 AC XY: 48AN XY: 727222
GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74334
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 23, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28719003) - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at