Variant 11-121086956-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001363644.2(TBCEL):c.1135C>T(p.Pro379Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 6.8e-7 ( 0 hom. )

Consequence

TBCEL
NM_001363644.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38

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:):

TBCEL-TECTA links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.118992984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TBCEL	NM_001363644.2 linkuse as main transcript	c.1135C>T	p.Pro379Ser	missense_variant	9/9	ENST00000683345.1	NP_001350573.1
TBCEL-TECTA	NM_001378761.1 linkuse as main transcript	c.957-15709C>T		intron_variant			NP_001365690.1
TBCEL	NM_001130047.3 linkuse as main transcript	c.1135C>T	p.Pro379Ser	missense_variant	8/8		NP_001123519.1
TBCEL	NM_152715.5 linkuse as main transcript	c.1135C>T	p.Pro379Ser	missense_variant	8/8		NP_689928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCEL	ENST00000683345.1 linkuse as main transcript	c.1135C>T	p.Pro379Ser	missense_variant	9/9		NM_001363644.2	ENSP00000507873	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461784

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2023

The c.1135C>T (p.P379S) alteration is located in exon 8 (coding exon 7) of the TBCEL gene. This alteration results from a C to T substitution at nucleotide position 1135, causing the proline (P) at amino acid position 379 to be replaced by a serine (S). 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

0.091

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

T;T

Eigen

Benign

-0.078

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.85

.;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.17

N;N

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Benign

0.089

Sift

Benign

0.17

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.0020

B;B

Vest4

0.084

MutPred

0.44

Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);

MVP

0.24

MPC

0.76

ClinPred

0.39

GERP RS

5.9

Varity_R

0.18

gMVP

0.57

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over