rs11097912

Variant names:

• chr4-106079305-C-T
• rs11097912
• NM_001163435.3:c.2571+16177G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• hypotonia, infantile, with psychomotor retardation and characteristic facies 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163435.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCK	NM_001163435.3	MANE Select	c.2571+16177G>A		intron	N/A	NP_001156907.2
	TBCK	NM_001163436.4		c.2571+16177G>A		intron	N/A	NP_001156908.2
	TBCK	NM_001163437.3		c.2454+16177G>A		intron	N/A	NP_001156909.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCK	ENST00000394708.7	TSL:1 MANE Select	c.2571+16177G>A		intron	N/A	ENSP00000378198.2
	TBCK	ENST00000394706.7	TSL:1	c.2454+16177G>A		intron	N/A	ENSP00000378196.3
	TBCK	ENST00000361687.8	TSL:1	c.2382+16177G>A		intron	N/A	ENSP00000355338.4

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

African (AFR) AF: 0.367 AC: 15204 AN: 41454

American (AMR) AF: 0.245 AC: 3744 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1072 AN: 3472

East Asian (EAS) AF: 0.141 AC: 728 AN: 5170

South Asian (SAS) AF: 0.313 AC: 1505 AN: 4812

European-Finnish (FIN) AF: 0.281 AC: 2961 AN: 10556

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22430 AN: 67950

Other (OTH) AF: 0.310 AC: 653 AN: 2108

Alfa AF: 0.328 Hom.: 3801

Bravo AF: 0.319

Asia WGS AF: 0.256 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.96
DANN	Benign	0.19
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11097912; hg19: chr4-107000462;