chr2-130191938-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_207312.3(TUBA3E):c.1246G>A(p.Gly416Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0022 in 1,614,070 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0020 ( 19 hom. )

Consequence

TUBA3E
NM_207312.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.19

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025752872).

BP6

Variant 2-130191938-C-T is Benign according to our data. Variant chr2-130191938-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651365.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00205 (2995/1461868) while in subpopulation MID AF= 0.0322 (186/5768). AF 95% confidence interval is 0.0285. There are 19 homozygotes in gnomad4_exome. There are 1633 alleles in male gnomad4_exome subpopulation. Median coverage is 74. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA3E	NM_207312.3 link	c.1246G>A	p.Gly416Arg	missense_variant	Exon 5 of 5	ENST00000312988.9	NP_997195.2	Q6PEY2
MZT2B	XM_047445914.1 link	c.319+9163C>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.1246G>A	p.Gly416Arg	missense_variant	Exon 5 of 5	1	NM_207312.3	ENSP00000318197.7		Q6PEY2

Frequencies

GnomAD3 genomes

AF:

0.00368

AC:

560

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00572

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00223

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00290

AC:

730

AN:

251466

Hom.:

AF XY:

0.00315

AC XY:

428

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00566

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00320

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00258

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00205

AC:

2995

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00225

AC XY:

1633

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00505

Gnomad4 AMR exome

AF:

0.00255

Gnomad4 ASJ exome

AF:

0.0130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00314

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00149

Gnomad4 OTH exome

AF:

0.00402

GnomAD4 genome

AF:

0.00369

AC:

562

AN:

152202

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

292

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00573

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00224

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00399

Hom.:

Bravo

AF:

0.00389

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.00396

AC:

ExAC

AF:

0.00301

AC:

366

EpiCase

AF:

0.00333

EpiControl

AF:

0.00433

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TUBA3E: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Pathogenic

0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.021

MetaRNN

Benign

0.026

MetaSVM

Uncertain

0.59

MutationAssessor

Pathogenic

3.9

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-5.2

REVEL

Pathogenic

0.76

Sift4G

Uncertain

0.028

Polyphen

1.0

Vest4

0.74

MutPred

0.48

Gain of solvent accessibility (P = 0.0306);

MVP

0.89

ClinPred

0.065

GERP RS

3.0

Varity_R

0.75

gMVP

0.54

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