Variant chr5-77691493-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000380377.9(TBCA):c.252T>A(p.Asn84Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

TBCA
ENST00000380377.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43

Variant links:

Genes affected

TBCA (HGNC:11579): (tubulin folding cofactor A) The product of this gene 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. This gene encodes chaperonin cofactor A. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

TBCA links:

TBCA (HGNC:):

TBCA 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=0.20031169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBCA	NM_004607.3 linkuse as main transcript	c.252T>A	p.Asn84Lys	missense_variant	4/4	ENST00000380377.9	NP_004598.1	O75347-1Q6FGD7
TBCA	NM_001297740.2 linkuse as main transcript	c.165T>A	p.Asn55Lys	missense_variant	3/3		NP_001284669.1	E5RIX8
TBCA	NM_001297738.2 linkuse as main transcript	c.*1629T>A		3_prime_UTR_variant	3/3		NP_001284667.1	O75347-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCA	ENST00000380377.9 linkuse as main transcript	c.252T>A	p.Asn84Lys	missense_variant	4/4	1	NM_004607.3	ENSP00000369736.4		O75347-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Dec 15, 2023

The c.252T>A (p.N84K) alteration is located in exon 4 (coding exon 4) of the TBCA gene. This alteration results from a T to A substitution at nucleotide position 252, causing the asparagine (N) at amino acid position 84 to be replaced by a lysine (K). 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

0.23

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.059

T;T;T;.;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.57

T;T;T;T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.20

T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.1

M;.;.;.;.

MutationTaster

Benign

0.98

D;D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.9

N;N;N;.;N

REVEL

Benign

0.13

Sift

Benign

0.56

T;T;T;.;T

Sift4G

Benign

0.73

T;T;T;T;T

Polyphen

0.014

B;.;.;.;.

Vest4

0.14

MutPred

0.42

Gain of ubiquitination at N84 (P = 0.0031);.;.;.;.;

MVP

0.42

MPC

0.44

ClinPred

0.76

GERP RS

4.6

Varity_R

0.32

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over