Genetic Variant TUBB6:c.-36C>T (chr18-12308257-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032525.3(TUBB6):c.-36C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,395,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TUBB6
NM_032525.3 5_prime_UTR_premature_start_codon_gain

Scores

Splicing: ADA: 0.00007055

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0180

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBB6	NM_032525.3 link	c.-36C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	ENST00000317702.10	NP_115914.1	Q9BUF5
TUBB6	NM_032525.3 link	c.-36C>T		5_prime_UTR_variant	Exon 1 of 4	ENST00000317702.10	NP_115914.1	Q9BUF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBB6	ENST00000317702 link	c.-36C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	1	NM_032525.3	ENSP00000318697.4		Q9BUF5
TUBB6	ENST00000317702 link	c.-36C>T		5_prime_UTR_variant	Exon 1 of 4	1	NM_032525.3	ENSP00000318697.4		Q9BUF5

Frequencies

GnomAD3 genomes

AF:

0.00000665

AC:

AN:

150466

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

112582

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1245164

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

615138

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25292

American (AMR)

AF:

0.00

AC:

AN:

25182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19802

East Asian (EAS)

AF:

0.00

AC:

AN:

25002

South Asian (SAS)

AF:

0.0000159

AC:

AN:

62900

European-Finnish (FIN)

AF:

0.0000283

AC:

AN:

35390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3394

European-Non Finnish (NFE)

AF:

0.0000140

AC:

AN:

999448

Other (OTH)

AF:

0.00

AC:

AN:

48754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000665

AC:

AN:

150466

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73424

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41242

American (AMR)

AF:

0.00

AC:

AN:

15102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67408

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.87

PromoterAI

-0.026

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000071

dbscSNV1_RF

Benign

0.0

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.

chr18-12308257-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over