Variant 12-49188909-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006009.4(TUBA1A):c.3+68A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,613,412 control chromosomes in the GnomAD database, including 103,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.32 ( 8565 hom., cov: 32)

Exomes 𝑓: 0.35 ( 94548 hom. )

Consequence

TUBA1A
NM_006009.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.20

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:

TUBA1C (HGNC:20768): (tubulin alpha 1c) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in microtubule cytoskeleton and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TUBA1C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-49188909-T-G is Benign according to our data. Variant chr12-49188909-T-G is described in ClinVar as [Benign]. Clinvar id is 1238419.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
TUBA1A	NM_006009.4 linkuse as main transcript	c.3+68A>C	intron_variant		ENST00000301071.12
TUBA1A	NM_001270399.2 linkuse as main transcript	c.-490A>C	5_prime_UTR_variant	1/4
TUBA1A	NM_001270400.2 linkuse as main transcript	c.-123A>C	5_prime_UTR_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBA1A	ENST00000301071.12 linkuse as main transcript	c.3+68A>C		intron_variant		1	NM_006009.4	P1	Q71U36-1

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48569

AN:

151690

Hom.:

8563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.311

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.715

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.409

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.308

GnomAD4 exome

AF:

0.350

AC:

512081

AN:

1461604

Hom.:

94548

Cov.:

AF XY:

0.353

AC XY:

256967

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.211

Gnomad4 AMR exome

AF:

0.319

Gnomad4 ASJ exome

AF:

0.242

Gnomad4 EAS exome

AF:

0.714

Gnomad4 SAS exome

AF:

0.472

Gnomad4 FIN exome

AF:

0.403

Gnomad4 NFE exome

AF:

0.334

Gnomad4 OTH exome

AF:

0.351

GnomAD4 genome

AF:

0.320

AC:

48586

AN:

151808

Hom.:

8565

Cov.:

AF XY:

0.328

AC XY:

24339

AN XY:

74176

show subpopulations

Gnomad4 AFR

AF:

0.223

Gnomad4 AMR

AF:

0.311

Gnomad4 ASJ

AF:

0.234

Gnomad4 EAS

AF:

0.715

Gnomad4 SAS

AF:

0.505

Gnomad4 FIN

AF:

0.409

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.306

Alfa

AF:

0.318

Hom.:

9018

Bravo

AF:

0.305

Asia WGS

AF:

0.557

AC:

1934

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.4

DANN

Benign

0.55

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