11-121053713-A-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_001363644.2(TBCEL):c.436A>T(p.Ile146Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000324 in 1,611,914 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

TBCEL
NM_001363644.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.75

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, TBCEL

BP4

Computational evidence support a benign effect (MetaRNN=0.006439328).

BP6

Variant 11-121053713-A-T is Benign according to our data. Variant chr11-121053713-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3035273.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 218 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TBCEL	NM_001363644.2 linkuse as main transcript	c.436A>T	p.Ile146Leu	missense_variant	5/9	ENST00000683345.1
TBCEL-TECTA	NM_001378761.1 linkuse as main transcript	c.436A>T	p.Ile146Leu	missense_variant	4/30
TBCEL	NM_001130047.3 linkuse as main transcript	c.436A>T	p.Ile146Leu	missense_variant	4/8
TBCEL	NM_152715.5 linkuse as main transcript	c.436A>T	p.Ile146Leu	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBCEL	ENST00000683345.1 linkuse as main transcript	c.436A>T	p.Ile146Leu	missense_variant	5/9		NM_001363644.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00144

AC:

218

AN:

151800

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00457

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00145

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000396

AC:

AN:

250178

Hom.:

AF XY:

0.000229

AC XY:

AN XY:

135232

show subpopulations

Gnomad AFR exome

AF:

0.00481

Gnomad AMR exome

AF:

0.000437

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000202

AC:

295

AN:

1459996

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

131

AN XY:

726308

show subpopulations

Gnomad4 AFR exome

AF:

0.00527

Gnomad4 AMR exome

AF:

0.000539

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.000730

GnomAD4 genome

AF:

0.00150

AC:

228

AN:

151918

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.00479

Gnomad4 AMR

AF:

0.00145

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000191

Hom.:

Bravo

AF:

0.00186

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000544

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TBCEL-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 11, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

Cadd

Benign

Dann

Benign

0.60

DEOGEN2

Benign

0.031

T;T;T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.0031

MetaRNN

Benign

0.0064

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.9

N;N;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.72

N;N;N;.

REVEL

Benign

0.067

Sift

Benign

1.0

T;T;T;.

Sift4G

Benign

1.0

T;T;T;.

Polyphen

0.0

B;B;.;.

Vest4

0.24

MutPred

0.27

Gain of catalytic residue at I146 (P = 0.0853);Gain of catalytic residue at I146 (P = 0.0853);Gain of catalytic residue at I146 (P = 0.0853);.;

MVP

0.24

MPC

0.75

ClinPred

0.029

GERP RS

3.7

Varity_R

0.092

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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