Genetic Variant TBKBP1:p.Pro189Pro (chr17-47698708-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001394755.1(TBKBP1):c.567C>T(p.Pro189Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000791 in 1,607,584 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00058 ( 4 hom. )

Consequence

TBKBP1
NM_001394755.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.594

Variant links:

Genes affected

TBKBP1 (HGNC:30140): (TBK1 binding protein 1) TBKBP1 is an adaptor protein that binds to TBK1 (MIM 604834) and is part of the interaction network in the TNF (MIM 191160)/NFKB (see MIM 164011) pathway (Bouwmeester et al., 2004 [PubMed 14743216]).[supplied by OMIM, Mar 2008]

TBKBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 17-47698708-C-T is Benign according to our data. Variant chr17-47698708-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2647876.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.594 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBKBP1	NM_001394755.1 link	c.567C>T	p.Pro189Pro	synonymous_variant	Exon 5 of 10	ENST00000578982.6	NP_001381684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBKBP1	ENST00000578982.6 link	c.567C>T	p.Pro189Pro	synonymous_variant	Exon 5 of 10	3	NM_001394755.1	ENSP00000462339.2	A7MCY6-1J3KS71
TBKBP1	ENST00000361722.7 link	c.567C>T	p.Pro189Pro	synonymous_variant	Exon 4 of 9	1		ENSP00000354777.3	A7MCY6-1
TBKBP1	ENST00000537587.6 link	c.567C>T	p.Pro189Pro	synonymous_variant	Exon 5 of 5	3		ENSP00000446365.2	F5H1U4

Frequencies

GnomAD3 genomes

AF:

0.00285

AC:

433

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00881

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.000972

AC:

231

AN:

237570

Hom.:

AF XY:

0.000784

AC XY:

101

AN XY:

128764

show subpopulations

Gnomad AFR exome

AF:

0.00884

Gnomad AMR exome

AF:

0.00179

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000347

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000363

Gnomad OTH exome

AF:

0.000864

GnomAD4 exome

AF:

0.000575

AC:

837

AN:

1455324

Hom.:

Cov.:

AF XY:

0.000535

AC XY:

387

AN XY:

723348

show subpopulations

Gnomad4 AFR exome

AF:

0.00996

Gnomad4 AMR exome

AF:

0.00175

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000472

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000326

Gnomad4 OTH exome

AF:

0.000848

GnomAD4 genome

AF:

0.00286

AC:

435

AN:

152260

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

210

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00883

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.00315

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TBKBP1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.36

DANN

Benign

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over