19-50384369-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002691.4(POLD1):c.-23C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 151,944 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002691.4 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.-23C>T | 5_prime_UTR_variant | Exon 1 of 27 | ENST00000440232.7 | NP_002682.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151944Hom.: 0 Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 322Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 248
GnomAD4 genome AF: 0.0000197 AC: 3AN: 151944Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2AN XY: 74200
ClinVar
Submissions by phenotype
not specified Uncertain:1
This variant is denoted POLD1 c.-23C>T, and describes a nucleotide substitution 23 base pairs upstream of the POLD1 ATG translational start site in the 5' untranslated region (UTR). The surrounding sequence, with the base that is substituted in braces, is GTGG[C/T]GGGA. This variant has not, to our knowledge, been reported in the literature as pathogenic or benign. This variant does not appear to affect the start codon or the Kozak translational consensus sequence. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The cytosine (C) nucleotide that is altered is conserved across species. At this time, we consider POLD1 c.-23C>T to be a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at