Variant 11-121053569-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_001363644.2(TBCEL):c.292A>C(p.Asn98His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000732 in 1,612,034 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 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

TBCEL
NM_001363644.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

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 Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, TBCEL

BP4

Computational evidence support a benign effect (MetaRNN=0.17401183).

BS2

High AC in GnomAd at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TBCEL	NM_001363644.2 linkuse as main transcript	c.292A>C	p.Asn98His	missense_variant	5/9	ENST00000683345.1
TBCEL-TECTA	NM_001378761.1 linkuse as main transcript	c.292A>C	p.Asn98His	missense_variant	4/30
TBCEL	NM_001130047.3 linkuse as main transcript	c.292A>C	p.Asn98His	missense_variant	4/8
TBCEL	NM_152715.5 linkuse as main transcript	c.292A>C	p.Asn98His	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBCEL	ENST00000683345.1 linkuse as main transcript	c.292A>C	p.Asn98His	missense_variant	5/9		NM_001363644.2	P1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151746

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

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:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000479

AC:

AN:

250624

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135446

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000692

AC:

101

AN:

1460170

Hom.:

Cov.:

AF XY:

0.0000661

AC XY:

AN XY:

726418

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000864

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.000112

AC:

AN:

151864

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.0000723

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:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

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

Aug 02, 2021

The c.292A>C (p.N98H) alteration is located in exon 4 (coding exon 3) of the TBCEL gene. This alteration results from a A to C substitution at nucleotide position 292, causing the asparagine (N) at amino acid position 98 to be replaced by a histidine (H). 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

-0.32

BayesDel_noAF

Benign

-0.48

Cadd

Uncertain

Dann

Uncertain

0.98

DEOGEN2

Benign

0.023

T;T;T;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

1.0

M_CAP

Benign

0.0072

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.23

N;N;N;.

REVEL

Benign

0.15

Sift

Benign

1.0

T;T;T;.

Sift4G

Benign

0.28

T;T;T;.

Polyphen

0.96

D;D;.;.

Vest4

0.28

MVP

0.53

MPC

1.6

ClinPred

0.46

GERP RS

6.2

Varity_R

0.35

gMVP

0.49

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