Variant chr10-133282258-C-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.2374G>T(p.Ala792Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,611,742 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: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TUBGCP2
NM_006659.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.484

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:

Genome browser will be placed here

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=0.03982547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP2	NM_006659.4 link	c.2374G>T	p.Ala792Ser	missense_variant	16/18	ENST00000252936.8	NP_006650.1	Q9BSJ2-1Q53EQ3
TUBGCP2	NM_001256617.2 link	c.2458G>T	p.Ala820Ser	missense_variant	17/19		NP_001243546.1	Q9BSJ2-4
TUBGCP2	NM_001256618.2 link	c.1984G>T	p.Ala662Ser	missense_variant	15/17		NP_001243547.1	Q9BSJ2-3
TUBGCP2	NR_046330.2 link	n.3094G>T		non_coding_transcript_exon_variant	16/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBGCP2	ENST00000252936.8 link	c.2374G>T	p.Ala792Ser	missense_variant	16/18	2	NM_006659.4	ENSP00000252936.3		Q9BSJ2-1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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

GnomAD3 exomes

AF:

0.0000328

AC:

AN:

243866

Hom.:

AF XY:

0.0000301

AC XY:

AN XY:

133012

show subpopulations

Gnomad AFR exome

AF:

0.000393

Gnomad AMR exome

AF:

0.0000585

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.0000151

AC:

AN:

1459412

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

725984

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.0000897

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:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.000263

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.000327

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:

0.000230

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 22, 2023

The c.2374G>T (p.A792S) alteration is located in exon 16 (coding exon 15) of the TUBGCP2 gene. This alteration results from a G to T substitution at nucleotide position 2374, causing the alanine (A) at amino acid position 792 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

Benign

0.079

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.056

T;.;.;T;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.85

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.52

.;T;T;T;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.040

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

N;.;.;N;.

PrimateAI

Benign

0.34

PROVEAN

Benign

0.68

N;N;N;N;N

REVEL

Benign

0.013

Sift

Benign

0.31

T;T;T;T;T

Sift4G

Benign

0.60

T;T;T;T;T

Polyphen

0.0010

B;.;.;B;.

Vest4

0.18

MVP

0.25

MPC

0.26

ClinPred

0.0085

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.021

gMVP

0.094

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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