chr12-132626309-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_006231.4(POLE):c.6339C>T(p.Ser2113=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,278 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S2113S) 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 -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.6339C>T | p.Ser2113= | synonymous_variant | 46/49 | ENST00000320574.10 | |
POLE | XM_011534795.4 | c.6339C>T | p.Ser2113= | synonymous_variant | 46/48 | ||
POLE | XM_011534797.4 | c.5418C>T | p.Ser1806= | synonymous_variant | 38/40 | ||
POLE | XM_011534802.4 | c.3327C>T | p.Ser1109= | synonymous_variant | 22/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.6339C>T | p.Ser2113= | synonymous_variant | 46/49 | 1 | NM_006231.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 152194Hom.: 0 Cov.: 33 FAILED QC
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249386Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135116
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461278Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726932
GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74346
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 25, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 18, 2021 | 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