Genetic Variant TUBB:c.57+21_57+22delTT (chr6-30720581-CTT-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_178014.4(TUBB):c.57+21_57+22delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000675 in 1,601,098 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 3 hom. )

Consequence

TUBB
NM_178014.4 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04

Publications

0 publications found

Variant links:

Genes affected

TUBB (HGNC:20778): (tubulin beta class I) This gene encodes a beta tubulin protein. This protein forms a dimer with alpha tubulin and acts as a structural component of microtubules. Mutations in this gene cause cortical dysplasia, complex, with other brain malformations 6. Alternative splicing results in multiple splice variants. There are multiple pseudogenes for this gene on chromosomes 1, 6, 7, 8, 9, and 13. [provided by RefSeq, Jun 2014]

TUBB Gene-Disease associations (from GenCC):

complex cortical dysplasia with other brain malformations 6
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
multiple benign circumferential skin creases on limbs 1
Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, G2P
TUBB3-related tubulinopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
multiple benign circumferential skin creases on limbs
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TUBB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 6-30720581-CTT-C is Benign according to our data. Variant chr6-30720581-CTT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 672680.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 562 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178014.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TUBB	NM_178014.4	MANE Select	c.57+21_57+22delTT	intron	N/A	NP_821133.1	Q5SU16
TUBB	NM_001293214.2		c.34+44_34+45delTT	intron	N/A	NP_001280143.1
TUBB	NM_001293213.2		c.57+21_57+22delTT	intron	N/A	NP_001280142.1	B4DMJ5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TUBB	ENST00000327892.13	TSL:1 MANE Select	c.57+19_57+20delTT	intron	N/A	ENSP00000339001.7	P07437
TUBB	ENST00000940307.1		c.57+19_57+20delTT	intron	N/A	ENSP00000610366.1
TUBB	ENST00000940306.1		c.57+19_57+20delTT	intron	N/A	ENSP00000610365.1

Frequencies

GnomAD3 genomes

AF:

0.00370

AC:

563

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00116

AC:

280

AN:

242094

AF XY:

0.000832

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000902

Gnomad OTH exome

AF:

0.000514

GnomAD4 exome

AF:

0.000358

AC:

518

AN:

1448784

Hom.:

AF XY:

0.000289

AC XY:

208

AN XY:

720332

show subpopulations

African (AFR)

AF:

0.0121

AC:

395

AN:

32708

American (AMR)

AF:

0.00197

AC:

AN:

41624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25684

East Asian (EAS)

AF:

0.00

AC:

AN:

39520

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53278

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00000362

AC:

AN:

1106022

Other (OTH)

AF:

0.000568

AC:

AN:

59826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00369

AC:

562

AN:

152314

Hom.:

Cov.:

AF XY:

0.00375

AC XY:

279

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0129

AC:

536

AN:

41570

American (AMR)

AF:

0.00118

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

111

139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000131

Hom.:

Bravo

AF:

0.00433

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over