chr15-43371382-A-G

Position:

chr15-43371382-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014444.5(TUBGCP4):c.28A>G(p.Ser10Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TUBGCP4
NM_014444.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24

Variant links:

Genes affected

TUBGCP4 (HGNC:16691): (tubulin gamma complex component 4) This gene encodes a component of the gamma-tubulin ring complex, which is required for microtubule nucleation. In mammalian cells, the protein localizes to centrosomes in association with gamma-tubulin. Crystal structure analysis revealed a structure composed of five helical bundles arranged around conserved hydrophobic cores. An exposed surface area located in the C-terminal domain is essential and sufficient for direct binding to gamma-tubulin. Mutations in this gene that alter microtubule organization are associated with microcephaly and chorioretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

TUBGCP4 links:

TUBGCP4 (HGNC:):

TUBGCP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4054557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP4	NM_014444.5 linkuse as main transcript	c.28A>G	p.Ser10Gly	missense_variant	1/18	ENST00000564079.6	NP_055259.2	Q9UGJ1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TUBGCP4	ENST00000564079.6 linkuse as main transcript	c.28A>G	p.Ser10Gly	missense_variant	1/18	1	NM_014444.5	ENSP00000456648.2	Q9UGJ1-2
TUBGCP4	ENST00000260383.11 linkuse as main transcript	c.28A>G	p.Ser10Gly	missense_variant	1/18	1		ENSP00000260383.7	Q9UGJ1-1
TUBGCP4	ENST00000563517.5 linkuse as main transcript	n.28A>G		non_coding_transcript_exon_variant	1/5	5		ENSP00000454696.1	H3BN56
TUBGCP4	ENST00000570081.1 linkuse as main transcript	n.293+1680A>G		intron_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000808

AC:

AN:

247542

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134570

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727206

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 08, 2022

This variant has not been reported in the literature in individuals affected with TUBGCP4-related conditions. This variant is present in population databases (rs759876258, gnomAD 0.002%). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 10 of the TUBGCP4 protein (p.Ser10Gly). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TUBGCP4 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

0.0093

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

T;.

Eigen

Benign

0.019

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.41

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.24

Sift

Benign

0.090

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.12

B;B

Vest4

0.26

MutPred

0.80

Loss of glycosylation at S10 (P = 0.0163);Loss of glycosylation at S10 (P = 0.0163);

MVP

0.27

MPC

0.16

ClinPred

0.52

GERP RS

5.0

Varity_R

0.68

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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