chr12-64464320-A-ATTT

Position:

• chr12-64464320-A-ATTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_013254.4(TBK1):​c.229-6_229-4dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000567 in 1,058,196 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: 0.000057 (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]

TBK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000567 (60/1058196) while in subpopulation AMR AF= 0.00021 (5/23842). AF 95% confidence interval is 0.0000826. There are 0 homozygotes in gnomad4_exome. There are 31 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 60 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBK1	NM_013254.4	c.229-6_229-4dupTTT		splice_region_variant, intron_variant		ENST00000331710.10	NP_037386.1
TBK1	XM_005268809.2	c.229-6_229-4dupTTT		splice_region_variant, intron_variant			XP_005268866.1
TBK1	XM_005268810.2	c.229-6_229-4dupTTT		splice_region_variant, intron_variant			XP_005268867.1
TBK1	XR_007063071.1	n.328-6_328-4dupTTT		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBK1	ENST00000331710.10	c.229-6_229-4dupTTT		splice_region_variant, intron_variant		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: 0.0000567 AC: 60 AN: 1058196 Hom.: 0 Cov.: 29 AF XY: 0.0000587 AC XY: 31 AN XY: 528148

Gnomad4 AFR exome AF: 0.0000408

Gnomad4 AMR exome AF: 0.000210

Gnomad4 ASJ exome AF: 0.000173

Gnomad4 EAS exome AF: 0.000104

Gnomad4 SAS exome AF: 0.0000831

Gnomad4 FIN exome AF: 0.0000567

Gnomad4 NFE exome AF: 0.0000463

Gnomad4 OTH exome AF: 0.0000695

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

Alfa AF: 0.00139 Hom.: 5204

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;