rs143102561
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_006231.4(POLE):c.1014C>T(p.Pro338=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000375 in 1,598,174 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. P338P) 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 -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.1014C>T | p.Pro338= | synonymous_variant | 10/49 | ENST00000320574.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.1014C>T | p.Pro338= | synonymous_variant | 10/49 | 1 | NM_006231.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152162Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000815 AC: 2AN: 245482Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132808
GnomAD4 exome AF: 0.0000367 AC: 53AN: 1445894Hom.: 0 Cov.: 30 AF XY: 0.0000319 AC XY: 23AN XY: 719984
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152280Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74454
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 18, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Apr 17, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jun 23, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 16, 2019 | 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