Genetic Variant TBCB:p.Pro9Leu (chr19-36115586-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001281.3(TBCB):c.26C>T(p.Pro9Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000168 in 1,609,766 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TBCB
NM_001281.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.55

Publications

0 publications found

Variant links:

Genes affected

TBCB (HGNC:1989): (tubulin folding cofactor B) Predicted to be involved in cell differentiation and nervous system development. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TBCB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBCB	NM_001281.3	MANE Select	c.26C>T	p.Pro9Leu	missense	Exon 1 of 6	NP_001272.2	Q99426-1
TBCB	NR_155756.2		n.620C>T		non_coding_transcript_exon	Exon 1 of 6
TBCB	NM_001300971.3		c.-382C>T		upstream_gene	N/A	NP_001287900.1	Q99426-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBCB	ENST00000221855.8	TSL:1 MANE Select	c.26C>T	p.Pro9Leu	missense	Exon 1 of 6	ENSP00000221855.3	Q99426-1
TBCB	ENST00000651435.1		c.26C>T	p.Pro9Leu	missense	Exon 1 of 7	ENSP00000498740.1	A0A494C0X0
TBCB	ENST00000888742.1		c.26C>T	p.Pro9Leu	missense	Exon 1 of 7	ENSP00000558801.1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000455

AC:

AN:

241926

AF XY:

0.0000380

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000206

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1457588

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

724714

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33348

American (AMR)

AF:

0.000202

AC:

AN:

44462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25988

East Asian (EAS)

AF:

0.00

AC:

AN:

39472

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85416

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1110376

Other (OTH)

AF:

0.0000332

AC:

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

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:

0.0000526

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41438

American (AMR)

AF:

0.000458

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

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:

0.00

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.32

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.54

MetaRNN

Uncertain

0.52

MetaSVM

Uncertain

0.50

MutationAssessor

Uncertain

2.3

PhyloP100

6.5

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.4

REVEL

Pathogenic

0.68

Sift

Uncertain

0.010

Sift4G

Uncertain

0.019

Polyphen

0.99

Vest4

0.41

MutPred

0.50

Gain of sheet (P = 0.0028)

MVP

0.97

MPC

0.72

ClinPred

0.88

GERP RS

5.4

PromoterAI

0.055

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.40

gMVP

0.39

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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