4-184657315-A-G
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_152683.4(PRIMPOL):c.175A>G(p.Lys59Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,607,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_152683.4 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Likely_benign. The variant received -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00000822 AC: 2AN: 243364 AF XY: 0.00000760 show subpopulations
GnomAD4 exome AF: 0.0000172 AC: 25AN: 1454950Hom.: 0 Cov.: 30 AF XY: 0.0000166 AC XY: 12AN XY: 723704 show subpopulations
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74358 show subpopulations
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: PRIMPOL c.175A>G (p.Lys59Glu) results in a conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change. The variant allele was found at a frequency of 8.2e-06 in 243364 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.175A>G in individuals affected with Myopia 22, Autosomal Dominant and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at