rs775134475
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_013254.4(TBK1):āc.1116A>Gā(p.Lys372=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,614,008 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 (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.000020 ( 0 hom. )
Consequence
TBK1
NM_013254.4 synonymous
NM_013254.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.73
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 -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 12-64484426-A-G is Benign according to our data. Variant chr12-64484426-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 571522.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.73 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 29 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBK1 | NM_013254.4 | c.1116A>G | p.Lys372= | synonymous_variant | 9/21 | ENST00000331710.10 | |
TBK1 | XM_005268809.2 | c.1116A>G | p.Lys372= | synonymous_variant | 9/21 | ||
TBK1 | XM_005268810.2 | c.1116A>G | p.Lys372= | synonymous_variant | 9/21 | ||
TBK1 | XR_007063071.1 | n.1215A>G | non_coding_transcript_exon_variant | 9/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBK1 | ENST00000331710.10 | c.1116A>G | p.Lys372= | synonymous_variant | 9/21 | 1 | NM_013254.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152160Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251298Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135834
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GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461848Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13AN XY: 727228
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74334
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 24, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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