chr12-49185913-C-G

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.453G>C(p.Ser151Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,612,662 control chromosomes in the GnomAD database, including 126,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 17126 hom., cov: 30)

Exomes 𝑓: 0.38 ( 108876 hom. )

Consequence

TUBA1A
NM_006009.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.300

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=1.1844239E-5).

BP6

Variant 12-49185913-C-G is Benign according to our data. Variant chr12-49185913-C-G is described in ClinVar as [Benign]. Clinvar id is 160157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49185913-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA1A	NM_006009.4 link	c.453G>C	p.Ser151Ser	synonymous_variant	Exon 4 of 4	ENST00000301071.12	NP_006000.2	Q71U36-1
TUBA1A	NM_001270399.2 link	c.453G>C	p.Ser151Ser	synonymous_variant	Exon 4 of 4		NP_001257328.1	Q71U36-1
TUBA1A	NM_001270400.2 link	c.348G>C	p.Ser116Ser	synonymous_variant	Exon 4 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.453G>C	p.Ser151Ser	synonymous_variant	Exon 4 of 4	1	NM_006009.4	ENSP00000301071.7		Q71U36-1

Frequencies

GnomAD3 genomes

AF:

0.453

AC:

68608

AN:

151586

Hom.:

17079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.648

Gnomad AMI

AF:

0.223

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.720

Gnomad SAS

AF:

0.550

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.345

Gnomad OTH

AF:

0.417

GnomAD3 exomes

AF:

0.416

AC:

104302

AN:

250668

Hom.:

23555

AF XY:

0.416

AC XY:

56424

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.649

Gnomad AMR exome

AF:

0.349

Gnomad ASJ exome

AF:

0.268

Gnomad EAS exome

AF:

0.736

Gnomad SAS exome

AF:

0.523

Gnomad FIN exome

AF:

0.403

Gnomad NFE exome

AF:

0.341

Gnomad OTH exome

AF:

0.382

GnomAD4 exome

AF:

0.377

AC:

550350

AN:

1460954

Hom.:

108876

Cov.:

AF XY:

0.379

AC XY:

275721

AN XY:

726792

show subpopulations

Gnomad4 AFR exome

AF:

0.655

Gnomad4 AMR exome

AF:

0.353

Gnomad4 ASJ exome

AF:

0.275

Gnomad4 EAS exome

AF:

0.715

Gnomad4 SAS exome

AF:

0.520

Gnomad4 FIN exome

AF:

0.404

Gnomad4 NFE exome

AF:

0.347

Gnomad4 OTH exome

AF:

0.393

GnomAD4 genome

AF:

0.453

AC:

68717

AN:

151708

Hom.:

17126

Cov.:

AF XY:

0.457

AC XY:

33894

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.648

Gnomad4 AMR

AF:

0.376

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.721

Gnomad4 SAS

AF:

0.550

Gnomad4 FIN

AF:

0.412

Gnomad4 NFE

AF:

0.345

Gnomad4 OTH

AF:

0.417

Alfa

AF:

0.317

Hom.:

2394

Bravo

AF:

0.454

TwinsUK

AF:

0.336

AC:

1245

ALSPAC

AF:

0.358

AC:

1379

ESP6500AA

AF:

0.642

AC:

2830

ESP6500EA

AF:

0.329

AC:

2826

ExAC

AF:

0.421

AC:

51082

EpiCase

AF:

0.337

EpiControl

AF:

0.328

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 07, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:3

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

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

- -

TUBA1A-related disorder

Benign:1

May 28, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.18

CADD

Benign

7.4

DANN

Benign

0.71

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.24

MetaRNN

Benign

0.000012

MetaSVM

Benign

-0.95

PROVEAN

Benign

-0.030

REVEL

Benign

0.044

Sift

Uncertain

0.0040

Sift4G

Benign

0.32

Vest4

0.081

ClinPred

0.011

GERP RS

0.17

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