Variant 10-5393521-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024803.3(TUBAL3):c.1337T>A(p.Phe446Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TUBAL3
NM_024803.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.985

Variant links:

Genes affected

TUBAL3 (HGNC:23534): (tubulin alpha like 3) 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. Predicted to be active in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

TUBAL3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09962806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBAL3	NM_024803.3 linkuse as main transcript	c.1337T>A	p.Phe446Tyr	missense_variant	4/4	ENST00000380419.8	NP_079079.1
TUBAL3	NM_001171864.2 linkuse as main transcript	c.1217T>A	p.Phe406Tyr	missense_variant	4/4		NP_001165335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBAL3	ENST00000380419.8 linkuse as main transcript	c.1337T>A	p.Phe446Tyr	missense_variant	4/4	1	NM_024803.3	ENSP00000369784	P1	A6NHL2-1
TUBAL3	ENST00000479328.1 linkuse as main transcript	c.1217T>A	p.Phe406Tyr	missense_variant	4/4	1		ENSP00000418799		A6NHL2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1447464

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718742

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2024

The c.1337T>A (p.F446Y) alteration is located in exon 4 (coding exon 4) of the TUBAL3 gene. This alteration results from a T to A substitution at nucleotide position 1337, causing the phenylalanine (F) at amino acid position 446 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

0.00093

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.033

T;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.37

T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.12

N;N

REVEL

Benign

0.14

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.54

T;T

Polyphen

0.072

B;B

Vest4

0.11

MutPred

0.28

Gain of phosphorylation at F446 (P = 0.0501);.;

MVP

0.66

MPC

0.12

ClinPred

0.30

GERP RS

0.45

Varity_R

0.21

gMVP

0.10

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over