Variant 11-121045812-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001363644.2(TBCEL):c.122C>T(p.Ser41Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,438,132 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TBCEL
NM_001363644.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCEL	NM_001363644.2 link	c.122C>T	p.Ser41Phe	missense_variant	Exon 3 of 9	ENST00000683345.1	NP_001350573.1
TBCEL-TECTA	NM_001378761.1 link	c.122C>T	p.Ser41Phe	missense_variant	Exon 2 of 30		NP_001365690.1
TBCEL	NM_001130047.3 link	c.122C>T	p.Ser41Phe	missense_variant	Exon 2 of 8		NP_001123519.1	Q5QJ74
TBCEL	NM_152715.5 link	c.122C>T	p.Ser41Phe	missense_variant	Exon 2 of 8		NP_689928.3	Q5QJ74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCEL	ENST00000683345.1 link	c.122C>T	p.Ser41Phe	missense_variant	Exon 3 of 9		NM_001363644.2	ENSP00000507873.1		Q5QJ74
TBCEL-TECTA	ENST00000645041.1 link	c.74C>T	p.Ser25Phe	missense_variant	Exon 1 of 10			ENSP00000496315.1		A0A2R8YFB7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000439

AC:

AN:

228022

Hom.:

AF XY:

0.00

AC XY:

AN XY:

123894

show subpopulations

Gnomad AFR exome

AF:

0.0000662

Gnomad AMR exome

AF:

0.00

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:

0.00000139

AC:

AN:

1438132

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715010

show subpopulations

Gnomad4 AFR exome

AF:

0.0000314

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.05e-7

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

Jul 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.122C>T (p.S41F) alteration is located in exon 2 (coding exon 1) of the TBCEL gene. This alteration results from a C to T substitution at nucleotide position 122, causing the serine (S) at amino acid position 41 to be replaced by a phenylalanine (F). 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

Pathogenic

0.71

BayesDel_addAF

Uncertain

0.099

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T;T;T;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

.;D;D;D;D

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.54

D;D;D;D;D

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.9

M;.;M;.;.

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.0

D;D;D;N;.

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

D;D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D;.

Polyphen

0.99

D;.;D;.;.

Vest4

0.72

MutPred

0.53

Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);.;

MVP

0.49

MPC

1.9

ClinPred

0.96

GERP RS

5.6

Varity_R

0.52

gMVP

0.72

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