Genetic Variant TBCB:p.Ile34Val (chr19-36115660-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001281.3(TBCB):c.100A>G(p.Ile34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,395,802 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TBCB
NM_001281.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.604

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:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14525697).

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.100A>G	p.Ile34Val	missense	Exon 1 of 6	NP_001272.2	Q99426-1
TBCB	NR_155756.2		n.694A>G		non_coding_transcript_exon	Exon 1 of 6
TBCB	NM_001300971.3		c.-308A>G		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.100A>G	p.Ile34Val	missense	Exon 1 of 6	ENSP00000221855.3	Q99426-1
TBCB	ENST00000651435.1		c.100A>G	p.Ile34Val	missense	Exon 1 of 7	ENSP00000498740.1	A0A494C0X0
TBCB	ENST00000888742.1		c.100A>G	p.Ile34Val	missense	Exon 1 of 7	ENSP00000558801.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1395802

Hom.:

Cov.:

AF XY:

0.00000433

AC XY:

AN XY:

692804

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31632

American (AMR)

AF:

0.00

AC:

AN:

42022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23728

East Asian (EAS)

AF:

0.00

AC:

AN:

33614

South Asian (SAS)

AF:

0.0000358

AC:

AN:

83814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47954

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5404

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1071180

Other (OTH)

AF:

0.00

AC:

AN:

56454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

0.078

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.036

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.67

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.3

PhyloP100

0.60

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.87

REVEL

Benign

0.24

Sift

Benign

0.13

Sift4G

Benign

0.36

Polyphen

0.0010

Vest4

0.078

MutPred

0.43

Gain of MoRF binding (P = 0.0919)

MVP

0.79

MPC

0.46

ClinPred

0.19

GERP RS

3.1

PromoterAI

-0.013

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.23

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over