11-121045700-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001363644.2(TBCEL):c.10C>A(p.Pro4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 1,594,022 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

TBCEL
NM_001363644.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05570078).

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCEL	NM_001363644.2 link	c.10C>A	p.Pro4Thr	missense_variant	Exon 3 of 9	ENST00000683345.1	NP_001350573.1
TBCEL-TECTA	NM_001378761.1 link	c.10C>A	p.Pro4Thr	missense_variant	Exon 2 of 30		NP_001365690.1
TBCEL	NM_001130047.3 link	c.10C>A	p.Pro4Thr	missense_variant	Exon 2 of 8		NP_001123519.1	Q5QJ74
TBCEL	NM_152715.5 link	c.10C>A	p.Pro4Thr	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.10C>A	p.Pro4Thr	missense_variant	Exon 3 of 9		NM_001363644.2	ENSP00000507873.1		Q5QJ74
TBCEL-TECTA	ENST00000645041.1 link	c.-39C>A		upstream_gene_variant				ENSP00000496315.1		A0A2R8YFB7

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000983

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

GnomAD2 exomes

AF:

0.0000300

AC:

AN:

233060

AF XY:

0.0000159

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000166

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000353

GnomAD4 exome

AF:

0.00000624

AC:

AN:

1442008

Hom.:

Cov.:

AF XY:

0.00000558

AC XY:

AN XY:

716286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32298

American (AMR)

AF:

0.000226

AC:

AN:

39772

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25008

East Asian (EAS)

AF:

0.00

AC:

AN:

39542

South Asian (SAS)

AF:

0.00

AC:

AN:

81398

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105630

Other (OTH)

AF:

0.00

AC:

AN:

59632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000125

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.0000967

AC:

AN:

41374

American (AMR)

AF:

0.000983

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.540

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000331

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 14, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.10C>A (p.P4T) alteration is located in exon 2 (coding exon 1) of the TBCEL gene. This alteration results from a C to A substitution at nucleotide position 10, causing the proline (P) at amino acid position 4 to be replaced by a threonine (T). 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

0.059

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.020

T;T;T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

.;T;T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.056

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.76

N;.;N;.

PhyloP100

1.4

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.54

N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.24

T;T;T;T

Sift4G

Benign

0.69

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.23

MVP

0.54

MPC

0.84

ClinPred

0.034

GERP RS

3.8

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.074

gMVP

0.28

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

11-121045700-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over