rs139607077
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_006231.4(POLE):c.6405C>T(p.Val2135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,896 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. V2135V) 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.6405C>T | p.Val2135= | synonymous_variant | 46/49 | ENST00000320574.10 | |
POLE | XM_011534795.4 | c.6405C>T | p.Val2135= | synonymous_variant | 46/48 | ||
POLE | XM_011534797.4 | c.5484C>T | p.Val1828= | synonymous_variant | 38/40 | ||
POLE | XM_011534802.4 | c.3393C>T | p.Val1131= | synonymous_variant | 22/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.6405C>T | p.Val2135= | synonymous_variant | 46/49 | 1 | NM_006231.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251062Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135768
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461578Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20AN XY: 727086
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152318Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74486
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 09, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | May 22, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 13, 2016 | 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