12-64464320-AT-ATTTTT

Variant names:

• chr12-64464320-A-ATTTT
• NM_013254.4:c.229-7_229-4dupTTTT

Variant summary

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

The NM_013254.4(TBK1):​c.229-7_229-4dupTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000189 in 1,059,416 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000019 (0 hom.)
  • Failed GnomAD Quality Control
• 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]

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 rank	MANE	Protein	UniProt
TBK1	NM_013254.4	c.229-7_229-4dupTTTT		splice_region_variant, intron_variant	Intron 3 of 20	ENST00000331710.10	NP_037386.1
TBK1	XM_005268809.2	c.229-7_229-4dupTTTT		splice_region_variant, intron_variant	Intron 3 of 20		XP_005268866.1
TBK1	XM_005268810.2	c.229-7_229-4dupTTTT		splice_region_variant, intron_variant	Intron 3 of 20		XP_005268867.1
TBK1	XR_007063071.1	n.328-7_328-4dupTTTT		splice_region_variant, intron_variant	Intron 3 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBK1	ENST00000331710.10	c.229-14_229-13insTTTT		intron_variant	Intron 3 of 20	1	NM_013254.4	ENSP00000329967.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 150546 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000189 AC: 2 AN: 1059416 Hom.: 0 Cov.: 29 AF XY: 0.00000189 AC XY: 1 AN XY: 528742

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000576

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000166

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 150546 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 73440

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-64858100;