Variant 2-131480421-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_080386.4(TUBA3D):c.728G>A(p.Arg243Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000113 in 1,588,352 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TUBA3D
NM_080386.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

Variant links:

Genes affected

TUBA3D (HGNC:24071): (tubulin alpha 3d) This gene encodes a member of the alpha tubulin family. Tubulin is a major component of microtubules, which are composed of alpha- and beta-tubulin heterodimers and microtubule-associated proteins in the cytoskeleton. Microtubules maintain cellular structure, function in intracellular transport, and play a role in spindle formation during mitosis. [provided by RefSeq, Oct 2011]

TUBA3D links:

MZT2A (HGNC:33187): (mitotic spindle organizing protein 2A) Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MZT2A links:

MZT2A (HGNC:):

MZT2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TUBA3D. . Gene score misZ 1.5331 (greater than the threshold 3.09). Trascript score misZ 3.5821 (greater than threshold 3.09). GenCC has associacion of gene with keratoconus 9.

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBA3D	NM_080386.4 linkuse as main transcript	c.728G>A	p.Arg243Gln	missense_variant	4/5	ENST00000321253.7	NP_525125.2	P0DPH8Q1ZYQ1
MZT2A	XM_047445568.1 linkuse as main transcript	c.623-8239C>T		intron_variant			XP_047301524.1
MZT2A	XM_005263742.4 linkuse as main transcript	c.320-8239C>T		intron_variant			XP_005263799.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TUBA3D	ENST00000321253.7 linkuse as main transcript	c.728G>A	p.Arg243Gln	missense_variant	4/5	1	NM_080386.4	ENSP00000326042.6	P0DPH8
MZT2A	ENST00000427024.5 linkuse as main transcript	n.278-8239C>T		intron_variant		3		ENSP00000403353.1	H7C202
MZT2A	ENST00000445782.2 linkuse as main transcript	n.331-8239C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000214

AC:

AN:

140326

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.000513

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247328

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

134096

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS 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:

0.0000104

AC:

AN:

1448026

Hom.:

Cov.:

AF XY:

0.00000971

AC XY:

AN XY:

720814

show subpopulations

Gnomad4 AFR exome

AF:

0.0000348

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000214

AC:

AN:

140326

Hom.:

Cov.:

AF XY:

0.0000146

AC XY:

AN XY:

68590

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.000513

ExAC

AF:

0.0000166

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

Dec 06, 2024

The c.728G>A (p.R243Q) alteration is located in exon 1 (coding exon 1) of the TUBA3D gene. This alteration results from a G to A substitution at nucleotide position 728, causing the arginine (R) at amino acid position 243 to be replaced by a glutamine (Q). 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

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.55

M_CAP

Benign

0.0088

MetaRNN

Uncertain

0.60

MetaSVM

Uncertain

-0.16

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.37

Sift4G

Uncertain

0.026

Vest4

0.50

MutPred

0.79

Loss of methylation at R243 (P = 0.0253);

MVP

0.35

ClinPred

0.91

GERP RS

-1.2

Varity_R

0.067

gMVP

0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over