Genetic Variant TUBB6:c.57+29C>A (chr18-12308378-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032525.3(TUBB6):c.57+29C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,367,594 control chromosomes in the GnomAD database, including 405,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 35851 hom., cov: 32)

Exomes 𝑓: 0.78 ( 369338 hom. )

Consequence

TUBB6
NM_032525.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0950

Publications

13 publications found

Variant links:

Genes affected

TUBB6 (HGNC:20776): (tubulin beta 6 class V) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

TUBB6 Gene-Disease associations (from GenCC):

facial palsy, congenital, with ptosis and velopharyngeal dysfunction
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TUBB6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 18-12308378-C-A is Benign according to our data. Variant chr18-12308378-C-A is described in ClinVar as Benign. ClinVar VariationId is 1684208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032525.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TUBB6	NM_032525.3	MANE Select	c.57+29C>A	intron	N/A	NP_115914.1	Q9BUF5
TUBB6	NM_001303524.1		c.57+29C>A	intron	N/A	NP_001290453.1	Q9BUF5
TUBB6	NM_001303526.2		c.57+29C>A	intron	N/A	NP_001290455.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TUBB6	ENST00000317702.10	TSL:1 MANE Select	c.57+29C>A	intron	N/A	ENSP00000318697.4	Q9BUF5
TUBB6	ENST00000591909.5	TSL:1	c.57+29C>A	intron	N/A	ENSP00000465040.1	K7EJ64
TUBB6	ENST00000586810.5	TSL:1	n.57+29C>A	intron	N/A	ENSP00000467348.1	K7EPE5

Frequencies

GnomAD3 genomes

AF:

0.675

AC:

101802

AN:

150914

Hom.:

35839

Cov.:

show subpopulations

Gnomad AFR

AF:

0.467

Gnomad AMI

AF:

0.718

Gnomad AMR

AF:

0.629

Gnomad ASJ

AF:

0.744

Gnomad EAS

AF:

0.610

Gnomad SAS

AF:

0.770

Gnomad FIN

AF:

0.817

Gnomad MID

AF:

0.723

Gnomad NFE

AF:

0.783

Gnomad OTH

AF:

0.675

GnomAD2 exomes

AF:

0.763

AC:

79109

AN:

103704

AF XY:

0.770

show subpopulations

Gnomad AFR exome

AF:

0.501

Gnomad AMR exome

AF:

0.629

Gnomad ASJ exome

AF:

0.754

Gnomad EAS exome

AF:

0.644

Gnomad FIN exome

AF:

0.826

Gnomad NFE exome

AF:

0.801

Gnomad OTH exome

AF:

0.758

GnomAD4 exome

AF:

0.776

AC:

944557

AN:

1216574

Hom.:

369338

Cov.:

AF XY:

0.777

AC XY:

464684

AN XY:

598014

show subpopulations

African (AFR)

AF:

0.466

AC:

11371

AN:

24394

American (AMR)

AF:

0.614

AC:

10743

AN:

17490

Ashkenazi Jewish (ASJ)

AF:

0.756

AC:

14052

AN:

18576

East Asian (EAS)

AF:

0.598

AC:

16039

AN:

26804

South Asian (SAS)

AF:

0.792

AC:

38595

AN:

48744

European-Finnish (FIN)

AF:

0.815

AC:

29482

AN:

36178

Middle Eastern (MID)

AF:

0.732

AC:

2430

AN:

3320

European-Non Finnish (NFE)

AF:

0.791

AC:

785615

AN:

992848

Other (OTH)

AF:

0.751

AC:

36230

AN:

48220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

9974

19948

29922

39896

49870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19918

39836

59754

79672

99590

<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:

0.674

AC:

101831

AN:

151020

Hom.:

35851

Cov.:

AF XY:

0.676

AC XY:

49898

AN XY:

73796

show subpopulations

African (AFR)

AF:

0.467

AC:

19286

AN:

41324

American (AMR)

AF:

0.628

AC:

9534

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.744

AC:

2574

AN:

3462

East Asian (EAS)

AF:

0.610

AC:

3115

AN:

5104

South Asian (SAS)

AF:

0.771

AC:

3723

AN:

4830

European-Finnish (FIN)

AF:

0.817

AC:

8372

AN:

10244

Middle Eastern (MID)

AF:

0.723

AC:

211

AN:

292

European-Non Finnish (NFE)

AF:

0.783

AC:

52949

AN:

67592

Other (OTH)

AF:

0.677

AC:

1418

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1543

3086

4628

6171

7714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.703

Hom.:

5813

Bravo

AF:

0.650

Asia WGS

AF:

0.661

AC:

2107

AN:

3192

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Facial palsy, congenital, with ptosis and velopharyngeal dysfunction (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.4

(source)

DANN

Benign

0.72

PhyloP100

-0.095

PromoterAI

-0.064

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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