4-106046684-G-GA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001163435.3(TBCK):c.2572-5_2572-4insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,362,466 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBCK NM_001163435.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.638

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 4-106046684-G-GA is Benign according to our data. Variant chr4-106046684-G-GA is described in ClinVar as [Benign]. Clinvar id is 1599218.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBCK	NM_001163435.3	c.2572-5_2572-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000394708.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBCK	ENST00000394708.7	c.2572-5_2572-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001163435.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 5 AN: 149904 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000490

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: 0.0000445

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00110 AC: 1503 AN: 1362466 Hom.: 0 Cov.: 22 AF XY: 0.00105 AC XY: 716 AN XY: 680668

Gnomad4 AFR exome AF: 0.00140

Gnomad4 AMR exome AF: 0.00171

Gnomad4 ASJ exome AF: 0.000531

Gnomad4 EAS exome AF: 0.000604

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.000773

Gnomad4 NFE exome AF: 0.00114

Gnomad4 OTH exome AF: 0.000851

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000400 AC: 6 AN: 150016 Hom.: 0 Cov.: 32 AF XY: 0.0000820 AC XY: 6 AN XY: 73198

Gnomad4 AFR AF: 0.0000733

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: 0.0000445

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 16, 2023

- -

Computational scores

Source: dbNSFP v4.3

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: rs771058414; hg19: chr4-106967841;