11-121053712-G-T

Position:

chr11-121053712-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001363644.2(TBCEL):c.435G>T(p.Met145Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000736 in 1,611,918 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 1 hom. )

Consequence

TBCEL
NM_001363644.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.110

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00575307).

BS2

High AC in GnomAd4 at 100 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBCEL	NM_001363644.2 link	c.435G>T	p.Met145Ile	missense_variant	5/9	ENST00000683345.1	NP_001350573.1
TBCEL-TECTA	NM_001378761.1 link	c.435G>T	p.Met145Ile	missense_variant	4/30		NP_001365690.1
TBCEL	NM_001130047.3 link	c.435G>T	p.Met145Ile	missense_variant	4/8		NP_001123519.1	Q5QJ74
TBCEL	NM_152715.5 link	c.435G>T	p.Met145Ile	missense_variant	4/8		NP_689928.3	Q5QJ74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCEL	ENST00000683345.1 link	c.435G>T	p.Met145Ile	missense_variant	5/9		NM_001363644.2	ENSP00000507873.1		Q5QJ74
TBCEL-TECTA	ENST00000645041.1 link	c.387G>T	p.Met129Ile	missense_variant	3/10			ENSP00000496315.1		A0A2R8YFB7

Frequencies

GnomAD3 genomes

AF:

0.000652

AC:

AN:

151806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00237

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:

0.000810

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.000588

AC:

147

AN:

250186

Hom.:

AF XY:

0.000592

AC XY:

AN XY:

135240

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000929

Gnomad NFE exome

AF:

0.000805

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000744

AC:

1086

AN:

1459994

Hom.:

Cov.:

AF XY:

0.000716

AC XY:

520

AN XY:

726314

show subpopulations

Gnomad4 AFR exome

AF:

0.000390

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000874

Gnomad4 OTH exome

AF:

0.000664

GnomAD4 genome

AF:

0.000658

AC:

100

AN:

151924

Hom.:

Cov.:

AF XY:

0.000660

AC XY:

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00236

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000825

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000650

Hom.:

Bravo

AF:

0.000910

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000453

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000601

EpiControl

AF:

0.00113

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

Jul 06, 2021

The c.435G>T (p.M145I) alteration is located in exon 4 (coding exon 3) of the TBCEL gene. This alteration results from a G to T substitution at nucleotide position 435, causing the methionine (M) at amino acid position 145 to be replaced by an isoleucine (I). 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

0.15

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.036

T;T;T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.17

.;T;T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.0058

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

N;N;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.74

N;N;N;.

REVEL

Benign

0.051

Sift

Benign

0.19

T;T;T;.

Sift4G

Benign

0.64

T;T;T;.

Polyphen

0.0

B;B;.;.

Vest4

0.17

MutPred

0.40

Gain of catalytic residue at L150 (P = 0.0568);Gain of catalytic residue at L150 (P = 0.0568);Gain of catalytic residue at L150 (P = 0.0568);.;

MVP

0.15

MPC

0.83

ClinPred

0.020

GERP RS

1.5

Varity_R

0.036

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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