rs1143560

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006009.4(TUBA1A):c.396C>T(p.Leu132Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,614,152 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 1 hom. )

Consequence

TUBA1A
NM_006009.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.46

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052078366).

BP6

Variant 12-49185970-G-A is Benign according to our data. Variant chr12-49185970-G-A is described in ClinVar as Benign. ClinVar VariationId is 160155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.46 with no splicing effect.

BS2

High AC in GnomAd4 at 214 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA1A	NM_006009.4 link	c.396C>T	p.Leu132Leu	synonymous_variant	Exon 4 of 4	ENST00000301071.12	NP_006000.2	Q71U36-1
TUBA1A	NM_001270399.2 link	c.396C>T	p.Leu132Leu	synonymous_variant	Exon 4 of 4		NP_001257328.1	Q71U36-1
TUBA1A	NM_001270400.2 link	c.291C>T	p.Leu97Leu	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.396C>T	p.Leu132Leu	synonymous_variant	Exon 4 of 4	1	NM_006009.4	ENSP00000301071.7		Q71U36-1

Frequencies

GnomAD3 genomes

AF:

0.00142

AC:

216

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00176

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00165

AC:

414

AN:

251410

AF XY:

0.00174

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00913

Gnomad EAS exome

AF:

0.000979

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.00173

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00155

AC:

2266

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1157

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.000777

AC:

AN:

33480

American (AMR)

AF:

0.00105

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00903

AC:

236

AN:

26136

East Asian (EAS)

AF:

0.000655

AC:

AN:

39700

South Asian (SAS)

AF:

0.000939

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00139

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00148

AC:

1650

AN:

1112008

Other (OTH)

AF:

0.00192

AC:

116

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

153

305

458

610

763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00141

AC:

214

AN:

152262

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

108

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.000553

AC:

AN:

41556

American (AMR)

AF:

0.00118

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5188

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00176

AC:

120

AN:

68002

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00184

Hom.:

Bravo

AF:

0.00137

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00162

AC:

197

EpiCase

AF:

0.00142

EpiControl

AF:

0.00237

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TUBA1A: BS1, BS2 -

Oct 31, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.27

CADD

Benign

1.9

(source)

DANN

Benign

0.78

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.29

M_CAP

Benign

0.012

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.99

PhyloP100

-1.5

PROVEAN

Benign

-1.8

REVEL

Benign

0.052

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.17

MVP

0.57

ClinPred

0.0079

GERP RS

-3.6

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over