chr12-64464320-A-ATTTTTTTTTTTTT

Position:

• chr12-64464320-A-ATTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013254.4(TBK1):​c.229-4_229-3insTTTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: TBK1 NM_013254.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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]

TBK1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBK1	NM_013254.4	c.229-4_229-3insTTTTTTTTTTTTT		splice_region_variant, intron_variant		ENST00000331710.10	NP_037386.1
TBK1	XM_005268809.2	c.229-4_229-3insTTTTTTTTTTTTT		splice_region_variant, intron_variant			XP_005268866.1
TBK1	XM_005268810.2	c.229-4_229-3insTTTTTTTTTTTTT		splice_region_variant, intron_variant			XP_005268867.1
TBK1	XR_007063071.1	n.328-4_328-3insTTTTTTTTTTTTT		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBK1	ENST00000331710.10	c.229-4_229-3insTTTTTTTTTTTTT		splice_region_variant, intron_variant		1	NM_013254.4	ENSP00000329967.5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs57810028; hg19: chr12-64858100;