12-49186397-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006009.4(TUBA1A):c.288A>G(p.Lys96Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,611,508 control chromosomes in the GnomAD database, including 128,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17587 hom., cov: 30)

Exomes 𝑓: 0.38 ( 110877 hom. )

Consequence

TUBA1A
NM_006009.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.912

Variant links:

Genes affected

TUBA1A (HGNC:20766): (tubulin alpha 1a) Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulins. The genes encoding these microtubule constituents belong to 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. There are multiple alpha and beta tubulin genes, which are highly conserved among species. This gene encodes alpha tubulin and is highly similar to the mouse and rat Tuba1 genes. Northern blot studies have shown that the gene expression is predominantly found in morphologically differentiated neurologic cells. This gene is one of three alpha-tubulin genes in a cluster on chromosome 12q. Mutations in this gene cause lissencephaly type 3 (LIS3) - a neurological condition characterized by microcephaly, intellectual disability, and early-onset epilepsy caused by defective neuronal migration. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2017]

TUBA1A links:

TUBA1B-AS1 (HGNC:56356): (TUBA1B antisense RNA 1)

TUBA1B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.4875958E-6).

BP6

Variant 12-49186397-T-C is Benign according to our data. Variant chr12-49186397-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 160154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49186397-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.912 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA1A	NM_006009.4 link	c.288A>G	p.Lys96Lys	synonymous_variant	Exon 3 of 4	ENST00000301071.12	NP_006000.2	Q71U36-1
TUBA1A	NM_001270399.2 link	c.288A>G	p.Lys96Lys	synonymous_variant	Exon 3 of 4		NP_001257328.1	Q71U36-1
TUBA1A	NM_001270400.2 link	c.183A>G	p.Lys61Lys	synonymous_variant	Exon 3 of 4		NP_001257329.1	Q71U36-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBA1A	ENST00000301071.12 link	c.288A>G	p.Lys96Lys	synonymous_variant	Exon 3 of 4	1	NM_006009.4	ENSP00000301071.7		Q71U36-1

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69357

AN:

151180

Hom.:

17540

Cov.:

show subpopulations

Gnomad AFR

AF:

0.664

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.380

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.721

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.415

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.420

GnomAD3 exomes

AF:

0.421

AC:

105865

AN:

251354

Hom.:

24608

AF XY:

0.421

AC XY:

57142

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.667

Gnomad AMR exome

AF:

0.360

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.742

Gnomad SAS exome

AF:

0.525

Gnomad FIN exome

AF:

0.410

Gnomad NFE exome

AF:

0.342

Gnomad OTH exome

AF:

0.385

GnomAD4 exome

AF:

0.379

AC:

553260

AN:

1460210

Hom.:

110877

Cov.:

AF XY:

0.381

AC XY:

277062

AN XY:

726440

show subpopulations

Gnomad4 AFR exome

AF:

0.672

Gnomad4 AMR exome

AF:

0.361

Gnomad4 ASJ exome

AF:

0.277

Gnomad4 EAS exome

AF:

0.718

Gnomad4 SAS exome

AF:

0.522

Gnomad4 FIN exome

AF:

0.410

Gnomad4 NFE exome

AF:

0.348

Gnomad4 OTH exome

AF:

0.396

GnomAD4 genome

AF:

0.459

AC:

69466

AN:

151298

Hom.:

17587

Cov.:

AF XY:

0.463

AC XY:

34236

AN XY:

73894

show subpopulations

Gnomad4 AFR

AF:

0.664

Gnomad4 AMR

AF:

0.381

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.722

Gnomad4 SAS

AF:

0.551

Gnomad4 FIN

AF:

0.415

Gnomad4 NFE

AF:

0.346

Gnomad4 OTH

AF:

0.421

Alfa

AF:

0.384

Hom.:

5244

Bravo

AF:

0.460

TwinsUK

AF:

0.335

AC:

1243

ALSPAC

AF:

0.358

AC:

1379

ESP6500AA

AF:

0.661

AC:

2911

ESP6500EA

AF:

0.330

AC:

2838

ExAC

AF:

0.426

AC:

51686

EpiCase

AF:

0.337

EpiControl

AF:

0.330

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 14, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:4

May 07, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Lissencephaly due to TUBA1A mutation

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.10

CADD

Benign

9.9

DANN

Benign

0.93

Eigen

Benign

-0.067

Eigen_PC

Benign

-0.027

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0000025

MetaSVM

Benign

-0.92

PROVEAN

Benign

-0.14

REVEL

Benign

0.065

Sift

Pathogenic

0.0

Sift4G

Benign

0.23

Vest4

0.047

ClinPred

0.039

GERP RS

3.4

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