Variant 16-89932544-A-AC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000315491.12(TUBB3):c.58-20dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 1,596,432 control chromosomes in the GnomAD database, including 655 homozygotes. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.021 ( 49 hom., cov: 33)

Exomes 𝑓: 0.022 ( 606 hom. )

Consequence

TUBB3
ENST00000315491.12 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.186

Variant links:

Genes affected

TUBB3 (HGNC:20772): (tubulin beta 3 class III) This gene encodes a class III member of the beta tubulin protein family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. This protein is primarily expressed in neurons and may be involved in neurogenesis and axon guidance and maintenance. Mutations in this gene are the cause of congenital fibrosis of the extraocular muscles type 3. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Oct 2010]

TUBB3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 16-89932544-A-AC is Benign according to our data. Variant chr16-89932544-A-AC is described in ClinVar as [Benign]. Clinvar id is 1175481.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB3	NM_006086.4 linkuse as main transcript	c.58-20dup		intron_variant		ENST00000315491.12	NP_006077.2
TUBB3	NM_001197181.2 linkuse as main transcript	c.-159-20dup		intron_variant			NP_001184110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB3	ENST00000315491.12 linkuse as main transcript	c.58-20dup		intron_variant		1	NM_006086.4	ENSP00000320295	P1	Q13509-1

Frequencies

GnomAD3 genomes

AF:

0.0209

AC:

3134

AN:

150300

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0216

Gnomad AMI

AF:

0.00991

Gnomad AMR

AF:

0.0182

Gnomad ASJ

AF:

0.0286

Gnomad EAS

AF:

0.00255

Gnomad SAS

AF:

0.0860

Gnomad FIN

AF:

0.00842

Gnomad MID

AF:

0.0160

Gnomad NFE

AF:

0.0194

Gnomad OTH

AF:

0.0233

GnomAD3 exomes

AF:

0.0239

AC:

5966

AN:

249880

Hom.:

145

AF XY:

0.0269

AC XY:

3642

AN XY:

135426

show subpopulations

Gnomad AFR exome

AF:

0.0214

Gnomad AMR exome

AF:

0.0120

Gnomad ASJ exome

AF:

0.0285

Gnomad EAS exome

AF:

0.00218

Gnomad SAS exome

AF:

0.0830

Gnomad FIN exome

AF:

0.0101

Gnomad NFE exome

AF:

0.0176

Gnomad OTH exome

AF:

0.0239

GnomAD4 exome

AF:

0.0217

AC:

31333

AN:

1446020

Hom.:

606

Cov.:

AF XY:

0.0234

AC XY:

16858

AN XY:

720354

show subpopulations

Gnomad4 AFR exome

AF:

0.0209

Gnomad4 AMR exome

AF:

0.0128

Gnomad4 ASJ exome

AF:

0.0265

Gnomad4 EAS exome

AF:

0.00134

Gnomad4 SAS exome

AF:

0.0795

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.0184

Gnomad4 OTH exome

AF:

0.0252

GnomAD4 genome

AF:

0.0209

AC:

3144

AN:

150412

Hom.:

Cov.:

AF XY:

0.0207

AC XY:

1521

AN XY:

73354

show subpopulations

Gnomad4 AFR

AF:

0.0217

Gnomad4 AMR

AF:

0.0184

Gnomad4 ASJ

AF:

0.0286

Gnomad4 EAS

AF:

0.00255

Gnomad4 SAS

AF:

0.0862

Gnomad4 FIN

AF:

0.00842

Gnomad4 NFE

AF:

0.0194

Gnomad4 OTH

AF:

0.0250

Asia WGS

AF:

0.0480

AC:

167

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

Feb 14, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

La Branchor

0.82

BranchPoint Hunter

3.0

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