Genetic Variant TUBB6:p.Arg121Trp (chr18-12325150-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_032525.3(TUBB6):c.361C>T(p.Arg121Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TUBB6
NM_032525.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.348

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.912

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBB6	NM_032525.3 link	c.361C>T	p.Arg121Trp	missense_variant	Exon 4 of 4	ENST00000317702.10	NP_115914.1	Q9BUF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBB6	ENST00000317702.10 link	c.361C>T	p.Arg121Trp	missense_variant	Exon 4 of 4	1	NM_032525.3	ENSP00000318697.4		Q9BUF5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460558

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726442

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

T;D;T;T

Eigen

Benign

-0.024

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.86

D;D;D;D

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.91

D;D;D;D

MetaSVM

Uncertain

0.38

MutationAssessor

Pathogenic

4.9

.;H;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-5.7

.;D;.;.

REVEL

Pathogenic

0.65

Sift

Pathogenic

0.0

.;D;.;.

Sift4G

Uncertain

0.0090

D;D;D;D

Polyphen

0.87

.;P;.;.

Vest4

0.89

MutPred

0.78

Gain of ubiquitination at K122 (P = 0.0613);Gain of ubiquitination at K122 (P = 0.0613);.;.;

MVP

0.88

MPC

2.1

ClinPred

1.0

GERP RS

-5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.77

gMVP

0.95

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over