11-121053551-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001363644.2(TBCEL):c.274G>A(p.Val92Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000267 in 1,611,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

TBCEL
NM_001363644.2 missense, splice_region

Scores

Splicing: ADA: 0.9986

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.78

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCEL	NM_001363644.2 link	c.274G>A	p.Val92Ile	missense_variant, splice_region_variant	Exon 5 of 9	ENST00000683345.1	NP_001350573.1
TBCEL-TECTA	NM_001378761.1 link	c.274G>A	p.Val92Ile	missense_variant, splice_region_variant	Exon 4 of 30		NP_001365690.1
TBCEL	NM_001130047.3 link	c.274G>A	p.Val92Ile	missense_variant, splice_region_variant	Exon 4 of 8		NP_001123519.1	Q5QJ74
TBCEL	NM_152715.5 link	c.274G>A	p.Val92Ile	missense_variant, splice_region_variant	Exon 4 of 8		NP_689928.3	Q5QJ74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCEL	ENST00000683345.1 link	c.274G>A	p.Val92Ile	missense_variant, splice_region_variant	Exon 5 of 9		NM_001363644.2	ENSP00000507873.1		Q5QJ74
TBCEL-TECTA	ENST00000645041.1 link	c.226G>A	p.Val76Ile	missense_variant, splice_region_variant	Exon 3 of 10			ENSP00000496315.1		A0A2R8YFB7

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151670

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.0000737

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000480

AC:

AN:

250010

AF XY:

0.0000518

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000797

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000290

AC:

423

AN:

1459524

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

197

AN XY:

726108

show subpopulations

African (AFR)

AF:

0.0000901

AC:

AN:

33314

American (AMR)

AF:

0.0000225

AC:

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26020

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.000372

AC:

413

AN:

1110532

Other (OTH)

AF:

0.0000996

AC:

AN:

60232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000462

AC:

AN:

151670

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74050

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41302

American (AMR)

AF:

0.00

AC:

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000737

AC:

AN:

67862

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.554

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000984

Hom.:

Bravo

AF:

0.0000604

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 05, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.274G>A (p.V92I) alteration is located in exon 4 (coding exon 3) of the TBCEL gene. This alteration results from a G to A substitution at nucleotide position 274, causing the valine (V) at amino acid position 92 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

0.084

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

T;T;T;.

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.88

.;D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.64

N;N;.;.

PhyloP100

7.8

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.27

N;N;N;.

REVEL

Benign

0.13

Sift

Benign

0.21

T;T;T;.

Sift4G

Benign

0.78

T;T;T;.

Polyphen

0.0020

B;B;.;.

Vest4

0.095

MVP

0.10

MPC

0.61

ClinPred

0.12

GERP RS

6.2

Varity_R

0.11

gMVP

0.50

Mutation Taster

=54/46

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Benign

0.69

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.30

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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11-121053551-G-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