Variant chr16-89932550-C-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_006086.4(TUBB3):c.58-21C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0048 in 1,608,064 control chromosomes in the GnomAD database, including 244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.024 ( 125 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 119 hom. )

Consequence

TUBB3
NM_006086.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.01

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=-0.79).

BP6

Variant 16-89932550-C-G is Benign according to our data. Variant chr16-89932550-C-G is described in ClinVar as [Benign]. Clinvar id is 1227568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-89932550-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0772 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.58-21C>G		intron_variant		ENST00000315491.12
TUBB3	NM_001197181.2 linkuse as main transcript	c.-159-21C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB3	ENST00000315491.12 linkuse as main transcript	c.58-21C>G		intron_variant		1	NM_006086.4	P1	Q13509-1

Frequencies

GnomAD3 genomes

AF:

0.0235

AC:

3578

AN:

152216

Hom.:

125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00692

AC:

1731

AN:

250308

Hom.:

AF XY:

0.00549

AC XY:

744

AN XY:

135588

show subpopulations

Gnomad AFR exome

AF:

0.0826

Gnomad AMR exome

AF:

0.00307

Gnomad ASJ exome

AF:

0.0203

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.000363

Gnomad OTH exome

AF:

0.00458

GnomAD4 exome

AF:

0.00284

AC:

4129

AN:

1455730

Hom.:

119

Cov.:

AF XY:

0.00255

AC XY:

1847

AN XY:

724594

show subpopulations

Gnomad4 AFR exome

AF:

0.0816

Gnomad4 AMR exome

AF:

0.00353

Gnomad4 ASJ exome

AF:

0.0215

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.000320

Gnomad4 NFE exome

AF:

0.000207

Gnomad4 OTH exome

AF:

0.00663

GnomAD4 genome

AF:

0.0235

AC:

3583

AN:

152334

Hom.:

125

Cov.:

AF XY:

0.0233

AC XY:

1732

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0795

Gnomad4 AMR

AF:

0.00804

Gnomad4 ASJ

AF:

0.0288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00332

Hom.:

Bravo

AF:

0.0262

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

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.50

DANN

Benign

0.91

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