Genetic Variant TUBA3E:p.Thr239Thr (chr2-130194125-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_207312.3(TUBA3E):c.717G>A(p.Thr239Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 152,178 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 12 hom. )

Failed GnomAD Quality Control

Consequence

TUBA3E
NM_207312.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.82

Variant links:

Genes affected

TUBA3E (HGNC:20765): (tubulin alpha 3e) Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. This gene encodes an alpha tubulin that highly conserved among species. A missense mutation in this gene has been potentially linked to microlissencephaly and global developmental delay. [provided by RefSeq, Jul 2016]

TUBA3E links:

MZT2B (HGNC:25886): (mitotic spindle organizing protein 2B) Located in cytosol; microtubule cytoskeleton; and nucleoplasm. Part of gamma-tubulin large complex. [provided by Alliance of Genome Resources, Apr 2022]

MZT2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 2-130194125-C-T is Benign according to our data. Variant chr2-130194125-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3770633.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.82 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA3E	NM_207312.3 link	c.717G>A	p.Thr239Thr	synonymous_variant	Exon 4 of 5	ENST00000312988.9	NP_997195.2	Q6PEY2
MZT2B	XM_047445914.1 link	c.320-8200C>T		intron_variant	Intron 2 of 3		XP_047301870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBA3E	ENST00000312988.9 link	c.717G>A	p.Thr239Thr	synonymous_variant	Exon 4 of 5	1	NM_207312.3	ENSP00000318197.7		Q6PEY2

Frequencies

GnomAD3 genomes

AF:

0.00355

AC:

540

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00354

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00632

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00396

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00147

AC:

368

AN:

250264

Hom.:

AF XY:

0.00140

AC XY:

189

AN XY:

135176

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00157

Gnomad ASJ exome

AF:

0.00416

Gnomad EAS exome

AF:

0.000545

Gnomad SAS exome

AF:

0.000951

Gnomad FIN exome

AF:

0.00312

Gnomad NFE exome

AF:

0.00132

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00176

AC:

2565

AN:

1457026

Hom.:

Cov.:

151

AF XY:

0.00182

AC XY:

1316

AN XY:

724888

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.00255

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.00143

Gnomad4 FIN exome

AF:

0.00698

Gnomad4 NFE exome

AF:

0.00133

Gnomad4 OTH exome

AF:

0.00256

GnomAD4 genome

AF:

0.00355

AC:

540

AN:

152178

Hom.:

Cov.:

AF XY:

0.00348

AC XY:

259

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00632

Gnomad4 NFE

AF:

0.00396

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00509

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TUBA3E: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.6

DANN

Benign

0.83

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