chr12-64455936-T-C
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_013254.4(TBK1):āc.66T>Cā(p.Asn22=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0431 in 1,613,322 control chromosomes in the GnomAD database, including 1,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.030 ( 116 hom., cov: 32)
Exomes š: 0.044 ( 1616 hom. )
Consequence
TBK1
NM_013254.4 synonymous
NM_013254.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.25
Genes affected
TBK1 (HGNC:11584): (TANK binding kinase 1) The NF-kappa-B (NFKB) complex of proteins is inhibited by I-kappa-B (IKB) proteins, which inactivate NFKB by trapping it in the cytoplasm. Phosphorylation of serine residues on the IKB proteins by IKB kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation and nuclear translocation of the NFKB complex. The protein encoded by this gene is similar to IKB kinases and can mediate NFKB activation in response to certain growth factors. The protein is also an important kinase for antiviral innate immunity response. [provided by RefSeq, Sep 2021]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant 12-64455936-T-C is Benign according to our data. Variant chr12-64455936-T-C is described in ClinVar as [Benign]. Clinvar id is 475941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-64455936-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=2.25 with no splicing effect.
BA1
GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBK1 | NM_013254.4 | c.66T>C | p.Asn22= | synonymous_variant | 2/21 | ENST00000331710.10 | |
TBK1 | XM_005268809.2 | c.66T>C | p.Asn22= | synonymous_variant | 2/21 | ||
TBK1 | XM_005268810.2 | c.66T>C | p.Asn22= | synonymous_variant | 2/21 | ||
TBK1 | XR_007063071.1 | n.165T>C | non_coding_transcript_exon_variant | 2/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBK1 | ENST00000331710.10 | c.66T>C | p.Asn22= | synonymous_variant | 2/21 | 1 | NM_013254.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0299 AC: 4551AN: 152216Hom.: 116 Cov.: 32
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GnomAD3 exomes AF: 0.0324 AC: 8119AN: 250762Hom.: 197 AF XY: 0.0340 AC XY: 4602AN XY: 135506
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GnomAD4 exome AF: 0.0445 AC: 64951AN: 1460988Hom.: 1616 Cov.: 30 AF XY: 0.0447 AC XY: 32480AN XY: 726770
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GnomAD4 genome AF: 0.0299 AC: 4554AN: 152334Hom.: 116 Cov.: 32 AF XY: 0.0297 AC XY: 2211AN XY: 74500
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 28, 2019 | - - |
Glaucoma 1, open angle, P Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | Jul 20, 2016 | - - |
Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
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