rs1376565938
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_007254.4(PNKP):c.663C>T(p.Ser221=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,622 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: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
PNKP
NM_007254.4 synonymous
NM_007254.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.800
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.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 19-49864045-G-A is Benign according to our data. Variant chr19-49864045-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 436349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.8 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNKP | NM_007254.4 | c.663C>T | p.Ser221= | synonymous_variant | 7/17 | ENST00000322344.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNKP | ENST00000322344.8 | c.663C>T | p.Ser221= | synonymous_variant | 7/17 | 1 | NM_007254.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
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33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250850Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135660
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461622Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727114
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GnomAD4 genome ? Cov.: 33
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Cov.:
33
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 10, 2016 | - - |
Developmental and epileptic encephalopathy, 12 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
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