Variant 12-49188874-G-A 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+103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0482 in 1,612,362 control chromosomes in the GnomAD database, including 2,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.037 ( 127 hom., cov: 32)

Exomes 𝑓: 0.049 ( 2148 hom. )

Consequence

TUBA1A
NM_006009.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.991

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 12-49188874-G-A is Benign according to our data. Variant chr12-49188874-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1207784.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
TUBA1A	NM_006009.4 linkuse as main transcript	c.3+103C>T	intron_variant		ENST00000301071.12
TUBA1A	NM_001270399.2 linkuse as main transcript	c.-455C>T	5_prime_UTR_variant	1/4
TUBA1A	NM_001270400.2 linkuse as main transcript	c.-103+15C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBA1A	ENST00000301071.12 linkuse as main transcript	c.3+103C>T		intron_variant		1	NM_006009.4	P1	Q71U36-1

Frequencies

GnomAD3 genomes

AF:

0.0367

AC:

5576

AN:

152126

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0476

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.0440

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0546

Gnomad OTH

AF:

0.0444

GnomAD4 exome

AF:

0.0495

AC:

72210

AN:

1460118

Hom.:

2148

Cov.:

AF XY:

0.0486

AC XY:

35287

AN XY:

726368

show subpopulations

Gnomad4 AFR exome

AF:

0.00887

Gnomad4 AMR exome

AF:

0.0326

Gnomad4 ASJ exome

AF:

0.0210

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00739

Gnomad4 FIN exome

AF:

0.0388

Gnomad4 NFE exome

AF:

0.0578

Gnomad4 OTH exome

AF:

0.0456

GnomAD4 genome

AF:

0.0366

AC:

5574

AN:

152244

Hom.:

127

Cov.:

AF XY:

0.0363

AC XY:

2701

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0110

Gnomad4 AMR

AF:

0.0475

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00601

Gnomad4 FIN

AF:

0.0440

Gnomad4 NFE

AF:

0.0546

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0339

Hom.:

Bravo

AF:

0.0366

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.4

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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