Variant 11-121055285-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001363644.2(TBCEL):c.689G>A(p.Arg230Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,457,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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

TBCEL
NM_001363644.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.81

Variant links:

Genes affected

TBCEL (HGNC:28115): (tubulin folding cofactor E like) Predicted to enable alpha-tubulin binding activity. Predicted to be involved in microtubule cytoskeleton organization; post-chaperonin tubulin folding pathway; and tubulin complex assembly. Predicted to be located in cytoskeleton. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TBCEL links:

TBCEL-TECTA (HGNC:54857): (TBCEL-TECTA readthrough) Predicted to enable alpha-tubulin binding activity. Predicted to be involved in microtubule cytoskeleton organization; post-chaperonin tubulin folding pathway; and tubulin complex assembly. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TBCEL-TECTA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37064528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCEL	NM_001363644.2 link	c.689G>A	p.Arg230Gln	missense_variant	Exon 6 of 9	ENST00000683345.1	NP_001350573.1
TBCEL-TECTA	NM_001378761.1 link	c.689G>A	p.Arg230Gln	missense_variant	Exon 5 of 30		NP_001365690.1
TBCEL	NM_001130047.3 link	c.689G>A	p.Arg230Gln	missense_variant	Exon 5 of 8		NP_001123519.1	Q5QJ74
TBCEL	NM_152715.5 link	c.689G>A	p.Arg230Gln	missense_variant	Exon 5 of 8		NP_689928.3	Q5QJ74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCEL	ENST00000683345.1 link	c.689G>A	p.Arg230Gln	missense_variant	Exon 6 of 9		NM_001363644.2	ENSP00000507873.1		Q5QJ74
TBCEL-TECTA	ENST00000645041.1 link	c.641G>A	p.Arg214Gln	missense_variant	Exon 4 of 10			ENSP00000496315.1		A0A2R8YFB7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

247932

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134008

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000206

AC:

AN:

1457710

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724996

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.0000769

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.689G>A (p.R230Q) alteration is located in exon 5 (coding exon 4) of the TBCEL gene. This alteration results from a G to A substitution at nucleotide position 689, causing the arginine (R) at amino acid position 230 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.046

T;T;T;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

.;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.37

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.7

L;L;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.6

N;N;N;.

REVEL

Benign

0.22

Sift

Benign

0.097

T;T;T;.

Sift4G

Uncertain

0.017

D;D;D;.

Polyphen

0.79

P;P;.;.

Vest4

0.43

MutPred

0.39

Loss of phosphorylation at S233 (P = 0.0613);Loss of phosphorylation at S233 (P = 0.0613);Loss of phosphorylation at S233 (P = 0.0613);.;

MVP

0.71

MPC

1.9

ClinPred

0.57

GERP RS

5.6

Varity_R

0.21

gMVP

0.63

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