rs61743676

Positions:

chr16-89935117-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_006086.4(TUBB3):c.666C>T(p.Tyr222Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,614,164 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 65 hom. )

Consequence

TUBB3
NM_006086.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.40

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:

ENSG00000198211 (HGNC:):

ENSG00000198211 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 16-89935117-C-T is Benign according to our data. Variant chr16-89935117-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 160194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89935117-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.4 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00116 (176/152340) while in subpopulation SAS AF= 0.0294 (142/4826). AF 95% confidence interval is 0.0255. There are 7 homozygotes in gnomad4. There are 110 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB3	NM_006086.4 linkuse as main transcript	c.666C>T	p.Tyr222Tyr	synonymous_variant	4/4	ENST00000315491.12	NP_006077.2	Q13509-1Q53G92
TUBB3	NM_001197181.2 linkuse as main transcript	c.450C>T	p.Tyr150Tyr	synonymous_variant	4/4		NP_001184110.1	Q13509-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB3	ENST00000315491.12 linkuse as main transcript	c.666C>T	p.Tyr222Tyr	synonymous_variant	4/4	1	NM_006086.4	ENSP00000320295.7		Q13509-1
ENSG00000198211	ENST00000556922.1 linkuse as main transcript	c.1707C>T	p.Tyr569Tyr	synonymous_variant	5/5	2		ENSP00000451560.1		A0A0B4J269

Frequencies

GnomAD3 genomes

AF:

0.00117

AC:

178

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0298

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00417

AC:

1049

AN:

251434

Hom.:

AF XY:

0.00564

AC XY:

767

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0319

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000378

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00209

AC:

3062

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00306

AC XY:

2226

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0317

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.00225

GnomAD4 genome

AF:

0.00116

AC:

176

AN:

152340

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

110

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0294

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000262

Hom.:

Bravo

AF:

0.000529

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 20, 2014	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 15, 2023	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 19, 2019	- -

TUBB3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.2

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