NM_006009.4:c.522G>A

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.522G>A(p.Ala174Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00694 in 1,610,752 control chromosomes in the GnomAD database, including 332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 150 hom., cov: 31)

Exomes 𝑓: 0.0048 ( 182 hom. )

Consequence

TUBA1A
NM_006009.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.240

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=0.0014648736).

BP6

Variant 12-49185844-C-T is Benign according to our data. Variant chr12-49185844-C-T is described in ClinVar as [Benign]. Clinvar id is 137850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49185844-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA1A	NM_006009.4 link	c.522G>A	p.Ala174Ala	synonymous_variant	Exon 4 of 4	ENST00000301071.12	NP_006000.2	Q71U36-1
TUBA1A	NM_001270399.2 link	c.522G>A	p.Ala174Ala	synonymous_variant	Exon 4 of 4		NP_001257328.1	Q71U36-1
TUBA1A	NM_001270400.2 link	c.417G>A	p.Ala139Ala	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.522G>A	p.Ala174Ala	synonymous_variant	Exon 4 of 4	1	NM_006009.4	ENSP00000301071.7		Q71U36-1

Frequencies

GnomAD3 genomes

AF:

0.0269

AC:

4082

AN:

151800

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0859

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00387

Gnomad OTH

AF:

0.0216

GnomAD3 exomes

AF:

0.00830

AC:

2084

AN:

251170

Hom.:

AF XY:

0.00699

AC XY:

950

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.0830

Gnomad AMR exome

AF:

0.00385

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00395

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00362

Gnomad OTH exome

AF:

0.00522

GnomAD4 exome

AF:

0.00484

AC:

7065

AN:

1458836

Hom.:

182

Cov.:

AF XY:

0.00459

AC XY:

3335

AN XY:

725830

show subpopulations

Gnomad4 AFR exome

AF:

0.0826

Gnomad4 AMR exome

AF:

0.00535

Gnomad4 ASJ exome

AF:

0.00444

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00370

Gnomad4 FIN exome

AF:

0.000805

Gnomad4 NFE exome

AF:

0.00288

Gnomad4 OTH exome

AF:

0.00692

GnomAD4 genome

AF:

0.0271

AC:

4116

AN:

151916

Hom.:

150

Cov.:

AF XY:

0.0268

AC XY:

1991

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.0865

Gnomad4 AMR

AF:

0.0121

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00387

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.00917

Hom.:

ESP6500AA

AF:

0.0749

AC:

330

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.0105

AC:

1275

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 31, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.31

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.83

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.98

PROVEAN

Benign

-0.48

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.080

ClinPred

0.030

GERP RS

4.4

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