4-184672207-T-C
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_152683.4(PRIMPOL):c.591T>C(p.Leu197=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,610,910 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 (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 0 hom. )
Consequence
PRIMPOL
NM_152683.4 synonymous
NM_152683.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.700
Genes affected
PRIMPOL (HGNC:26575): (primase and DNA directed polymerase) This gene encodes a DNA primase-polymerase that belongs to a superfamily of archaeao-eukaryotic primases. Members of this family have primase activity, catalyzing the synthesis of short RNA primers that serve as starting points for DNA synthesis, as well as DNA polymerase activity. The encoded protein facilitates DNA damage tolerance by mediating uninterrupted fork progression after UV irradiation and reinitiating DNA synthesis. An allelic variant in this gene is associated with myopia 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 4-184672207-T-C is Benign according to our data. Variant chr4-184672207-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3039377.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.7 with no splicing effect.
BS2
?
High AC in GnomAd at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRIMPOL | NM_152683.4 | c.591T>C | p.Leu197= | synonymous_variant | 7/14 | ENST00000314970.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRIMPOL | ENST00000314970.11 | c.591T>C | p.Leu197= | synonymous_variant | 7/14 | 1 | NM_152683.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152220Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000564 AC: 14AN: 248100Hom.: 0 AF XY: 0.0000671 AC XY: 9AN XY: 134062
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GnomAD4 exome AF: 0.000204 AC: 298AN: 1458690Hom.: 0 Cov.: 32 AF XY: 0.000185 AC XY: 134AN XY: 725562
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74358
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PRIMPOL-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 23, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at