rs772384393
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_002691.4(POLD1):c.363C>A(p.Ser121=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,458 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S121S) has been classified as Likely benign.
Frequency
Consequence
NM_002691.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.363C>A | p.Ser121= | synonymous_variant | 4/27 | ENST00000440232.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLD1 | ENST00000440232.7 | c.363C>A | p.Ser121= | synonymous_variant | 4/27 | 1 | NM_002691.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250262Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135452
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461458Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3AN XY: 727078
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Colorectal cancer, susceptibility to, 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2017 | This sequence change affects codon 121 of the POLD1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the POLD1 protein. This variant is present in population databases (rs772384393, ExAC 0.006%) but has not been reported in the literature in individuals with a POLD1-related disease. In summary, this is a rare silent change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at