Variant rs752790319 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003193.5(TBCE):c.841C>G(p.Gln281Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TBCE
NM_003193.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.765

Variant links:

Genes affected

TBCE (HGNC:11582): (tubulin folding cofactor E) Cofactor E is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

TBCE links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10815278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TBCE	NM_003193.5 linkuse as main transcript	c.841C>G	p.Gln281Glu	missense_variant	10/17	ENST00000642610.2	NP_003184.1
TBCE	NM_001287801.2 linkuse as main transcript	c.994C>G	p.Gln332Glu	missense_variant	11/18		NP_001274730.1
TBCE	NM_001079515.3 linkuse as main transcript	c.841C>G	p.Gln281Glu	missense_variant	10/17		NP_001072983.1
TBCE	NM_001287802.2 linkuse as main transcript	c.502C>G	p.Gln168Glu	missense_variant	9/16		NP_001274731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCE	ENST00000642610.2 linkuse as main transcript	c.841C>G	p.Gln281Glu	missense_variant	10/17		NM_003193.5	ENSP00000494796	P1	Q15813-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251356

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135900

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461420

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727036

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.095

.;T;T;T;T;T;.;T;T;T;.;.;.;.;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.56

.;.;.;.;.;.;.;.;.;.;T;T;D;T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.11

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;L;L;L;L;L;.;L;L;L;.;.;.;.;.

MutationTaster

Benign

0.95

D;D;D

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

.;.;.;.;.;.;.;.;.;N;.;.;N;.;.

REVEL

Benign

0.074

Sift

Benign

0.37

.;.;.;.;.;.;.;.;.;T;.;.;T;.;.

Sift4G

Benign

0.33

.;.;.;.;.;.;.;.;.;T;.;.;T;.;.

Polyphen

0.014

.;B;B;B;B;B;.;B;B;B;.;.;.;.;.

Vest4

0.31, 0.35

MutPred

0.34

.;Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);.;.;.;Loss of helix (P = 0.079);

MVP

0.27

MPC

0.23

ClinPred

0.057

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.063

gMVP

0.45

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over