chr4-184678240-A-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_152683.4(PRIMPOL):c.853A>G(p.Thr285Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000542 in 1,574,426 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00041 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00056 ( 2 hom. )
Consequence
PRIMPOL
NM_152683.4 missense
NM_152683.4 missense
Scores
6
9
3
Clinical Significance
Conservation
PhyloP100: 8.10
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 Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAd at 63 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRIMPOL | NM_152683.4 | c.853A>G | p.Thr285Ala | missense_variant | 8/14 | ENST00000314970.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRIMPOL | ENST00000314970.11 | c.853A>G | p.Thr285Ala | missense_variant | 8/14 | 1 | NM_152683.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000414 AC: 63AN: 152198Hom.: 1 Cov.: 32
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?
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GnomAD3 exomes AF: 0.000308 AC: 66AN: 214506Hom.: 0 AF XY: 0.000256 AC XY: 30AN XY: 117386
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GnomAD4 exome AF: 0.000555 AC: 790AN: 1422228Hom.: 2 Cov.: 28 AF XY: 0.000524 AC XY: 370AN XY: 706700
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GnomAD4 genome ? AF: 0.000414 AC: 63AN: 152198Hom.: 1 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74362
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ExAC
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 10, 2023 | The c.853A>G (p.T285A) alteration is located in exon 8 (coding exon 6) of the PRIMPOL gene. This alteration results from a A to G substitution at nucleotide position 853, causing the threonine (T) at amino acid position 285 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;.;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;.;D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at