rs11097912

chr4-106079305-C-T

Variant summary

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

The NM_001163435.3(TBCK):c.2571+16177G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,994 control chromosomes in the GnomAD database, including 8,010 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 0.32 (8010 hom., cov: 32)
• Consequence: TBCK NM_001163435.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBCK	NM_001163435.3	c.2571+16177G>A		intron_variant		ENST00000394708.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBCK	ENST00000394708.7	c.2571+16177G>A		intron_variant		1	NM_001163435.3	P1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48664 AN: 151876 Hom.: 7995 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.311

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.321 AC: 48722 AN: 151994 Hom.: 8010 Cov.: 32 AF XY: 0.315 AC XY: 23413 AN XY: 74292

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.310

Alfa AF: 0.331 Hom.: 2109

Bravo AF: 0.319

Asia WGS AF: 0.256 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.96
Dann	Benign	0.19

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs11097912; hg19: chr4-107000462;