Genetic Variant TUBB3:c.58-20dupC (chr16-89932544-A-AC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_006086.4(TUBB3):c.58-20dupC 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
NM_006086.4 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:

ENSG00000198211 (HGNC:):

ENSG00000198211 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TUBB3	NM_006086.4 link	c.58-20dupC		intron_variant	Intron 1 of 3	ENST00000315491.12	NP_006077.2	Q13509-1Q53G92
TUBB3	NM_001197181.2 link	c.-159-20dupC		intron_variant	Intron 1 of 3		NP_001184110.1	Q13509-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBB3	ENST00000315491.12 link	c.58-20dupC		intron_variant	Intron 1 of 3	1	NM_006086.4	ENSP00000320295.7		Q13509-1
ENSG00000198211	ENST00000556922.1 link	c.1099-20dupC		intron_variant	Intron 2 of 4	2		ENSP00000451560.1		A0A0B4J269

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

GnomAD2 exomes

AF:

0.0239

AC:

5966

AN:

249880

AF XY:

0.0269

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 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

AC:

691

AN:

33138

Gnomad4 AMR exome

AF:

0.0128

AC:

573

AN:

44698

Gnomad4 ASJ exome

AF:

0.0265

AC:

689

AN:

26044

Gnomad4 EAS exome

AF:

0.00134

AC:

AN:

39626

Gnomad4 SAS exome

AF:

0.0795

AC:

6837

AN:

85948

Gnomad4 FIN exome

AF:

0.0105

AC:

558

AN:

52978

Gnomad4 NFE exome

AF:

0.0184

AC:

20220

AN:

1098014

Gnomad4 Remaining exome

AF:

0.0252

AC:

1505

AN:

59830

Heterozygous variant carriers

1444

2888

4331

5775

7219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

822

1644

2466

3288

4110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

AC:

0.0216536

AN:

0.0216536

Gnomad4 AMR

AF:

0.0184

AC:

0.0183505

AN:

0.0183505

Gnomad4 ASJ

AF:

0.0286

AC:

0.0286293

AN:

0.0286293

Gnomad4 EAS

AF:

0.00255

AC:

0.00255302

AN:

0.00255302

Gnomad4 SAS

AF:

0.0862

AC:

0.086163

AN:

0.086163

Gnomad4 FIN

AF:

0.00842

AC:

0.00842311

AN:

0.00842311

Gnomad4 NFE

AF:

0.0194

AC:

0.0193699

AN:

0.0193699

Gnomad4 OTH

AF:

0.0250

AC:

0.024952

AN:

0.024952

Heterozygous variant carriers

160

320

479

639

799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0138

Hom.:

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

Feb 14, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

La Branchor

0.82

BranchPoint Hunter

3.0

Mutation Taster

=300/0

polymorphism (auto)

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