dbSNP rs1047706820: TBKBP1:p.Ser217Pro (chr17-47699334-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001394755.1(TBKBP1):c.649T>C(p.Ser217Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000367 in 1,526,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S217F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

TBKBP1
NM_001394755.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.605

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02694118).

BP6

Variant 17-47699334-T-C is Benign according to our data. Variant chr17-47699334-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2258383.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394755.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBKBP1	NM_001394755.1	MANE Select	c.649T>C	p.Ser217Pro	missense	Exon 6 of 10	NP_001381684.1	A7MCY6-1
TBKBP1	NM_001394756.1		c.649T>C	p.Ser217Pro	missense	Exon 6 of 10	NP_001381685.1	A7MCY6-1
TBKBP1	NM_014726.2		c.649T>C	p.Ser217Pro	missense	Exon 5 of 9	NP_055541.1	A7MCY6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBKBP1	ENST00000578982.6	TSL:3 MANE Select	c.649T>C	p.Ser217Pro	missense	Exon 6 of 10	ENSP00000462339.2	A7MCY6-1
TBKBP1	ENST00000361722.7	TSL:1	c.649T>C	p.Ser217Pro	missense	Exon 5 of 9	ENSP00000354777.3	A7MCY6-1
TBKBP1	ENST00000851181.1		c.649T>C	p.Ser217Pro	missense	Exon 6 of 10	ENSP00000521240.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000568

AC:

AN:

175990

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000378

AC:

AN:

1374582

Hom.:

Cov.:

AF XY:

0.0000369

AC XY:

AN XY:

677590

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30128

American (AMR)

AF:

0.00

AC:

AN:

30370

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20980

East Asian (EAS)

AF:

0.00

AC:

AN:

38472

South Asian (SAS)

AF:

0.0000136

AC:

AN:

73268

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3748

European-Non Finnish (NFE)

AF:

0.0000465

AC:

AN:

1074304

Other (OTH)

AF:

0.0000177

AC:

AN:

56368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151916

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41342

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

67958

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.85

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.0073

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0068

LIST_S2

Benign

0.24

M_CAP

Benign

0.0052

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.55

PhyloP100

-0.60

PrimateAI

Uncertain

0.59

PROVEAN

Benign

1.8

REVEL

Benign

0.032

Sift

Benign

1.0

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.20

MutPred

0.15

Loss of phosphorylation at S217 (P = 0.0258)

MVP

0.095

MPC

0.48

ClinPred

0.021

GERP RS

1.2

Varity_R

0.097

gMVP

0.094

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over