Variant chr16-89932522-C-T 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_006086.4(TUBB3):c.58-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 1,513,978 control chromosomes in the GnomAD database, including 13,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.18 ( 5170 hom., cov: 33)

Exomes 𝑓: 0.079 ( 7921 hom. )

Consequence

TUBB3
NM_006086.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -3.00

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 16-89932522-C-T is Benign according to our data. Variant chr16-89932522-C-T is described in ClinVar as [Benign]. Clinvar id is 160193.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB3	NM_006086.4 linkuse as main transcript	c.58-49C>T		intron_variant		ENST00000315491.12
TUBB3	NM_001197181.2 linkuse as main transcript	c.-159-49C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB3	ENST00000315491.12 linkuse as main transcript	c.58-49C>T		intron_variant		1	NM_006086.4	P1	Q13509-1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28105

AN:

152132

Hom.:

5151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.476

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0963

Gnomad EAS

AF:

0.00461

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.0289

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.0703

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.0978

AC:

24337

AN:

248808

Hom.:

2614

AF XY:

0.0940

AC XY:

12673

AN XY:

134864

show subpopulations

Gnomad AFR exome

AF:

0.482

Gnomad AMR exome

AF:

0.0694

Gnomad ASJ exome

AF:

0.0984

Gnomad EAS exome

AF:

0.000871

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.0285

Gnomad NFE exome

AF:

0.0738

Gnomad OTH exome

AF:

0.0983

GnomAD4 exome

AF:

0.0788

AC:

107254

AN:

1361728

Hom.:

7921

Cov.:

AF XY:

0.0796

AC XY:

54338

AN XY:

683010

show subpopulations

Gnomad4 AFR exome

AF:

0.492

Gnomad4 AMR exome

AF:

0.0767

Gnomad4 ASJ exome

AF:

0.0985

Gnomad4 EAS exome

AF:

0.00790

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.0320

Gnomad4 NFE exome

AF:

0.0648

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.185

AC:

28155

AN:

152250

Hom.:

5170

Cov.:

AF XY:

0.179

AC XY:

13319

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.476

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.0963

Gnomad4 EAS

AF:

0.00462

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.0289

Gnomad4 NFE

AF:

0.0702

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.113

Hom.:

528

Bravo

AF:

0.203

Asia WGS

AF:

0.0910

AC:

317

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

- -

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

-0.89

CADD

Benign

0.28

DANN

Benign

0.74

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