Variant 5-77691482-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004607.3(TBCA):c.263T>C(p.Leu88Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000486 in 1,440,178 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: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

TBCA
NM_004607.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.66

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBCA	NM_004607.3 linkuse as main transcript	c.263T>C	p.Leu88Ser	missense_variant	4/4	ENST00000380377.9	NP_004598.1	O75347-1Q6FGD7
TBCA	NM_001297740.2 linkuse as main transcript	c.176T>C	p.Leu59Ser	missense_variant	3/3		NP_001284669.1	E5RIX8
TBCA	NM_001297738.2 linkuse as main transcript	c.*1640T>C		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.263T>C	p.Leu88Ser	missense_variant	4/4	1	NM_004607.3	ENSP00000369736.4		O75347-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000486

AC:

AN:

1440178

Hom.:

Cov.:

AF XY:

0.00000698

AC XY:

AN XY:

716118

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:

0.00000633

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000624

Hom.:

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

Jun 18, 2024

The c.263T>C (p.L88S) alteration is located in exon 4 (coding exon 4) of the TBCA gene. This alteration results from a T to C substitution at nucleotide position 263, causing the leucine (L) at amino acid position 88 to be replaced by a serine (S). 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

Pathogenic

0.64

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T;T;.;T

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D;T;D;D

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.78

D;D;D;D;D

MetaSVM

Benign

-0.33

MutationAssessor

Uncertain

2.7

M;.;.;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-5.9

D;D;D;.;D

REVEL

Uncertain

0.50

Sift

Benign

0.058

T;T;D;.;D

Sift4G

Benign

0.17

T;D;D;T;T

Polyphen

1.0

D;.;.;.;.

Vest4

0.62

MutPred

0.73

Gain of phosphorylation at L88 (P = 0.0075);.;.;.;.;

MVP

0.41

MPC

1.4

ClinPred

1.0

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

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

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