rs697624

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. S151S) has been classified as Likely 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

Publications

24 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 -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 VariationId is 160157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

GnomAD2 exomes

AF:

0.416

AC:

104302

AN:

250668

AF XY:

0.416

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 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

African (AFR)

AF:

0.655

AC:

21858

AN:

33384

American (AMR)

AF:

0.353

AC:

15732

AN:

44578

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

7172

AN:

26114

East Asian (EAS)

AF:

0.715

AC:

28359

AN:

39664

South Asian (SAS)

AF:

0.520

AC:

44836

AN:

86232

European-Finnish (FIN)

AF:

0.404

AC:

21585

AN:

53382

Middle Eastern (MID)

AF:

0.270

AC:

1557

AN:

5768

European-Non Finnish (NFE)

AF:

0.347

AC:

385537

AN:

1111472

Other (OTH)

AF:

0.393

AC:

23714

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

20074

40149

60223

80298

100372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12660

25320

37980

50640

63300

<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:

0.453

AC:

68717

AN:

151708

Hom.:

17126

Cov.:

AF XY:

0.457

AC XY:

33894

AN XY:

74092

show subpopulations

African (AFR)

AF:

0.648

AC:

26807

AN:

41344

American (AMR)

AF:

0.376

AC:

5727

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

932

AN:

3468

East Asian (EAS)

AF:

0.721

AC:

3695

AN:

5126

South Asian (SAS)

AF:

0.550

AC:

2645

AN:

4812

European-Finnish (FIN)

AF:

0.412

AC:

4332

AN:

10522

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.345

AC:

23421

AN:

67904

Other (OTH)

AF:

0.417

AC:

876

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1747

3494

5242

6989

8736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.317

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

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

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

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.18

CADD

Benign

7.4

(source)

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

PhyloP100

0.30

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

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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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