Variant 10-133279833-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006659.4(TUBGCP2):c.2642C>T(p.Thr881Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,196 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TUBGCP2
NM_006659.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.475

Variant links:

Genes affected

TUBGCP2 (HGNC:18599): (tubulin gamma complex component 2) Predicted to enable gamma-tubulin binding activity. Predicted to contribute to microtubule minus-end binding activity. Involved in brain development and neuron migration. Located in centrosome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TUBGCP2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.064855754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP2	NM_006659.4 link	c.2642C>T	p.Thr881Ile	missense_variant	18/18	ENST00000252936.8	NP_006650.1	Q9BSJ2-1Q53EQ3
TUBGCP2	NM_001256617.2 link	c.2726C>T	p.Thr909Ile	missense_variant	19/19		NP_001243546.1	Q9BSJ2-4
TUBGCP2	NM_001256618.2 link	c.2252C>T	p.Thr751Ile	missense_variant	17/17		NP_001243547.1	Q9BSJ2-3
TUBGCP2	NR_046330.2 link	n.3362C>T		non_coding_transcript_exon_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBGCP2	ENST00000252936.8 link	c.2642C>T	p.Thr881Ile	missense_variant	18/18	2	NM_006659.4	ENSP00000252936.3		Q9BSJ2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000458

AC:

AN:

218118

Hom.:

AF XY:

0.00000840

AC XY:

AN XY:

119082

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000633

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1444196

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717398

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.05e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 15, 2024

The c.2642C>T (p.T881I) alteration is located in exon 18 (coding exon 17) of the TUBGCP2 gene. This alteration results from a C to T substitution at nucleotide position 2642, causing the threonine (T) at amino acid position 881 to be replaced by an isoleucine (I). 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

0.072

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.5

DANN

Benign

0.94

DEOGEN2

Benign

0.068

T;.;.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.40

.;T;T;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.065

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.;N;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.32

N;N;N;N;N

REVEL

Benign

0.018

Sift

Uncertain

0.016

D;D;D;D;D

Sift4G

Benign

0.12

T;T;T;T;T

Polyphen

0.0020

B;.;.;B;.

Vest4

0.034

MutPred

0.24

Loss of glycosylation at T881 (P = 0.0112);.;.;Loss of glycosylation at T881 (P = 0.0112);.;

MVP

0.32

MPC

0.31

ClinPred

0.045

GERP RS

-0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.026

gMVP

0.20

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