rs148382941
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6
The NM_006231.4(POLE):āc.2818A>Gā(p.Met940Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M940I) 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 -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.2818A>G | p.Met940Val | missense_variant | 24/49 | ENST00000320574.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.2818A>G | p.Met940Val | missense_variant | 24/49 | 1 | NM_006231.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251486Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135916
GnomAD4 exome AF: 0.0000369 AC: 54AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.0000385 AC XY: 28AN XY: 727242
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74338
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 23, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with neuroblastoma or advanced cancer undergoing multi-gene panel testing (Zhang et al., 2015; Mandelker et al., 2017); This variant is associated with the following publications: (PMID: 23292937, 28873162, 26580448, 20951805) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at