chr19-49862520-A-AG
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_007254.4(PNKP):c.936+17_936+18insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,605,176 control chromosomes in the GnomAD database, including 169 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.011 ( 23 hom., cov: 32)
Exomes 𝑓: 0.012 ( 146 hom. )
Consequence
PNKP
NM_007254.4 intron
NM_007254.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.889
Genes affected
PNKP (HGNC:9154): (polynucleotide kinase 3'-phosphatase) This locus represents a gene involved in DNA repair. In response to ionizing radiation or oxidative damage, the protein encoded by this locus catalyzes 5' phosphorylation and 3' dephosphorylation of nucleic acids. Mutations at this locus have been associated with microcephaly, seizures, and developmental delay.[provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP6
Variant 19-49862520-A-AG is Benign according to our data. Variant chr19-49862520-A-AG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 206371.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=3}.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0106 (1608/152224) while in subpopulation AMR AF= 0.0286 (438/15300). AF 95% confidence interval is 0.0264. There are 23 homozygotes in gnomad4. There are 759 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 23 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNKP | NM_007254.4 | c.936+17_936+18insC | intron_variant | ENST00000322344.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNKP | ENST00000322344.8 | c.936+17_936+18insC | intron_variant | 1 | NM_007254.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0106 AC: 1612AN: 152106Hom.: 23 Cov.: 32
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GnomAD3 exomes AF: 0.0109 AC: 2507AN: 229218Hom.: 21 AF XY: 0.0113 AC XY: 1414AN XY: 124942
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GnomAD4 exome AF: 0.0123 AC: 17873AN: 1452952Hom.: 146 Cov.: 35 AF XY: 0.0124 AC XY: 8938AN XY: 722230
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GnomAD4 genome AF: 0.0106 AC: 1608AN: 152224Hom.: 23 Cov.: 32 AF XY: 0.0102 AC XY: 759AN XY: 74412
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, flagged submission | clinical testing | GeneDx | Mar 19, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Developmental and epileptic encephalopathy, 12 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at