Variant 11-121055174-G-A 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.578G>A(p.Arg193Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,736 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

TBCEL
NM_001363644.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.98

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TBCEL	NM_001363644.2 linkuse as main transcript	c.578G>A	p.Arg193Gln	missense_variant	6/9	ENST00000683345.1	NP_001350573.1
TBCEL-TECTA	NM_001378761.1 linkuse as main transcript	c.578G>A	p.Arg193Gln	missense_variant	5/30		NP_001365690.1
TBCEL	NM_001130047.3 linkuse as main transcript	c.578G>A	p.Arg193Gln	missense_variant	5/8		NP_001123519.1
TBCEL	NM_152715.5 linkuse as main transcript	c.578G>A	p.Arg193Gln	missense_variant	5/8		NP_689928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCEL	ENST00000683345.1 linkuse as main transcript	c.578G>A	p.Arg193Gln	missense_variant	6/9		NM_001363644.2	ENSP00000507873	P1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151736

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151736

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74096

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 21, 2023

The c.578G>A (p.R193Q) 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 578, causing the arginine (R) at amino acid position 193 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

0.092

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.034

T;T;T;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

.;D;D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.48

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.8

M;M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.58

N;N;N;.

REVEL

Benign

0.22

Sift

Benign

0.084

T;T;T;.

Sift4G

Benign

0.15

T;T;D;.

Polyphen

1.0

D;D;.;.

Vest4

0.43

MutPred

0.56

Gain of ubiquitination at K194 (P = 0.0872);Gain of ubiquitination at K194 (P = 0.0872);Gain of ubiquitination at K194 (P = 0.0872);.;

MVP

0.67

MPC

1.8

ClinPred

0.90

GERP RS

5.0

Varity_R

0.20

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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