Variant chr1-235380138-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003193.5(TBCE):c.89C>T(p.Pro30Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TBCE
NM_003193.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.824

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TBCE	NM_003193.5 linkuse as main transcript	c.89C>T	p.Pro30Leu	missense_variant	2/17	ENST00000642610.2
TBCE	NM_001287801.2 linkuse as main transcript	c.89C>T	p.Pro30Leu	missense_variant	2/18
TBCE	NM_001079515.3 linkuse as main transcript	c.89C>T	p.Pro30Leu	missense_variant	2/17
TBCE	NM_001287802.2 linkuse as main transcript	c.-222C>T		5_prime_UTR_variant	2/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBCE	ENST00000642610.2 linkuse as main transcript	c.89C>T	p.Pro30Leu	missense_variant	2/17		NM_003193.5	P1	Q15813-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459428

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726028

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Pituitary stalk interruption syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Human Developmental Genetics, Institut Pasteur

Sep 10, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

D;D;D;D;D;.;.;D;D;D;.;.;.;.;.;.;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

.;.;.;.;.;.;.;.;.;.;D;D;D;D;D;D;D

M_CAP

Benign

0.056

MetaRNN

Pathogenic

0.82

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.028

MutationAssessor

Uncertain

2.1

M;M;M;M;M;.;.;M;M;M;.;.;.;.;M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-6.0

.;.;.;.;.;.;.;.;.;D;.;.;.;.;D;D;.

REVEL

Uncertain

0.49

Sift

Uncertain

0.025

.;.;.;.;.;.;.;.;.;D;.;.;.;.;D;D;.

Sift4G

Uncertain

0.0050

.;.;.;.;.;.;.;.;.;D;.;.;.;.;D;D;.

Polyphen

0.42

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

Vest4

0.57, 0.57, 0.57

MutPred

0.74

Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);Loss of catalytic residue at P30 (P = 0.0222);

MVP

0.84

MPC

0.81

ClinPred

0.99

GERP RS

5.5

Varity_R

0.27

gMVP

0.69

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over