12-132632728-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_006231.4(POLE):c.6072C>T(p.Pro2024=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,298 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P2024P) has been classified as Likely benign.
Frequency
Consequence
NM_006231.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.6072C>T | p.Pro2024= | synonymous_variant | 44/49 | ENST00000320574.10 | |
POLE | XM_011534795.4 | c.6072C>T | p.Pro2024= | synonymous_variant | 44/48 | ||
POLE | XM_011534797.4 | c.5151C>T | p.Pro1717= | synonymous_variant | 36/40 | ||
POLE | XM_011534802.4 | c.3060C>T | p.Pro1020= | synonymous_variant | 20/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.6072C>T | p.Pro2024= | synonymous_variant | 44/49 | 1 | NM_006231.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152064Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249486Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135322
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461234Hom.: 1 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 726946
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152064Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74272
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 21, 2019 | This variant is associated with the following publications: (PMID: 28577310) - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 23, 2015 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at