Variant chr16-89932549-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000315491.12(TUBB3):c.58-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 1,607,320 control chromosomes in the GnomAD database, including 13,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 5057 hom., cov: 33)

Exomes 𝑓: 0.078 ( 8294 hom. )

Consequence

TUBB3
ENST00000315491.12 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.623

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 16-89932549-C-T is Benign according to our data. Variant chr16-89932549-C-T is described in ClinVar as [Benign]. Clinvar id is 160192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89932549-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 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.58-22C>T		intron_variant		ENST00000315491.12	NP_006077.2
TUBB3	NM_001197181.2 linkuse as main transcript	c.-159-22C>T		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.58-22C>T		intron_variant		1	NM_006086.4	ENSP00000320295	P1	Q13509-1

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27880

AN:

152128

Hom.:

5038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0962

Gnomad EAS

AF:

0.00519

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.0289

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.0701

Gnomad OTH

AF:

0.172

GnomAD3 exomes

AF:

0.0979

AC:

24491

AN:

250192

Hom.:

2616

AF XY:

0.0942

AC XY:

12769

AN XY:

135552

show subpopulations

Gnomad AFR exome

AF:

0.477

Gnomad AMR exome

AF:

0.0691

Gnomad ASJ exome

AF:

0.0984

Gnomad EAS exome

AF:

0.00125

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.0288

Gnomad NFE exome

AF:

0.0741

Gnomad OTH exome

AF:

0.0981

GnomAD4 exome

AF:

0.0782

AC:

113777

AN:

1455076

Hom.:

8294

Cov.:

AF XY:

0.0791

AC XY:

57266

AN XY:

724326

show subpopulations

Gnomad4 AFR exome

AF:

0.487

Gnomad4 AMR exome

AF:

0.0763

Gnomad4 ASJ exome

AF:

0.0983

Gnomad4 EAS exome

AF:

0.00804

Gnomad4 SAS exome

AF:

0.125

Gnomad4 FIN exome

AF:

0.0321

Gnomad4 NFE exome

AF:

0.0644

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.183

AC:

27930

AN:

152244

Hom.:

5057

Cov.:

AF XY:

0.177

AC XY:

13215

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.471

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.0962

Gnomad4 EAS

AF:

0.00520

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.0289

Gnomad4 NFE

AF:

0.0701

Gnomad4 OTH

AF:

0.171

Alfa

AF:

0.0812

Hom.:

558

Bravo

AF:

0.201

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.84

DANN

Benign

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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