rs571119317
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_007254.4(PNKP):c.624C>T(p.Ala208=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,614,148 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 4 hom. )
Consequence
PNKP
NM_007254.4 synonymous
NM_007254.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.10
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 19-49864191-G-A is Benign according to our data. Variant chr19-49864191-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211921.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1, Likely_benign=2}. Variant chr19-49864191-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-5.1 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNKP | NM_007254.4 | c.624C>T | p.Ala208= | synonymous_variant | 6/17 | ENST00000322344.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNKP | ENST00000322344.8 | c.624C>T | p.Ala208= | synonymous_variant | 6/17 | 1 | NM_007254.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152198Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000314 AC: 79AN: 251332Hom.: 1 AF XY: 0.000390 AC XY: 53AN XY: 135878
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GnomAD4 exome AF: 0.000178 AC: 260AN: 1461832Hom.: 4 Cov.: 33 AF XY: 0.000263 AC XY: 191AN XY: 727214
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GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74472
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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 provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2022 | PNKP: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 01, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 18, 2014 | - - |
Developmental and epileptic encephalopathy, 12 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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