rs12639869

Positions:

• chr4-106254947-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290768.2(TBCK):​c.-62G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 164,326 control chromosomes in the GnomAD database, including 1,906 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1703 hom., cov: 32)
  • Exomes 𝑓: 0.18 (203 hom.)
• Consequence: TBCK NM_001290768.2 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.000007043
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.728

Genes affected

TBCK (HGNC:28261): (TBC1 domain containing kinase) This gene encodes a protein that contains a protein kinase domain, a Rhodanase-like domain and the Tre-2/Bub2/Cdc16 (TBC) domain. The encoded protein is thought to play a role in actin organization, cell growth and cell proliferation by regulating the mammalian target of the rapamycin (mTOR) signaling pathway. This protein may also be involved in the transcriptional regulation of the components of the mTOR complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

TBCK (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBCK	NM_001163435.3	c.456-2940G>T		intron_variant		ENST00000394708.7	NP_001156907.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCK	ENST00000394708.7	c.456-2940G>T		intron_variant		1	NM_001163435.3	ENSP00000378198.2

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21423 AN: 151338 Hom.: 1709 Cov.: 32

Gnomad AFR AF: 0.0699

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.176 AC: 2260 AN: 12872 Hom.: 203 Cov.: 0 AF XY: 0.179 AC XY: 1548 AN XY: 8636

Gnomad4 AFR exome AF: 0.0870

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.194

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.141 AC: 21418 AN: 151454 Hom.: 1703 Cov.: 32 AF XY: 0.143 AC XY: 10563 AN XY: 74022

Gnomad4 AFR AF: 0.0699

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.129

Alfa AF: 0.153 Hom.: 329

Bravo AF: 0.130

Asia WGS AF: 0.203 AC: 704 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	12
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000070
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12639869; hg19: chr4-107176104;