Variant 2-131480451-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_080386.4(TUBA3D):c.758C>T(p.Thr253Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,589,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TUBA3D
NM_080386.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.26

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, TUBA3D

BP4

Computational evidence support a benign effect (MetaRNN=0.23722506).

BS2

High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TUBA3D	NM_080386.4 linkuse as main transcript	c.758C>T	p.Thr253Met	missense_variant	4/5	ENST00000321253.7
MZT2A	XM_005263742.4 linkuse as main transcript	c.320-8269G>A		intron_variant
MZT2A	XM_047445568.1 linkuse as main transcript	c.623-8269G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TUBA3D	ENST00000321253.7 linkuse as main transcript	c.758C>T	p.Thr253Met	missense_variant	4/5	1	NM_080386.4	P1
MZT2A	ENST00000427024.5 linkuse as main transcript	c.279-8269G>A		intron_variant, NMD_transcript_variant		3
MZT2A	ENST00000445782.2 linkuse as main transcript	n.331-8269G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000214

AC:

AN:

140246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000320

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000214

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000364

AC:

AN:

247262

Hom.:

AF XY:

0.0000373

AC XY:

AN XY:

134090

show subpopulations

Gnomad AFR exome

AF:

0.0000742

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000145

AC:

AN:

1448964

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

721336

show subpopulations

Gnomad4 AFR exome

AF:

0.0000691

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000543

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000214

AC:

AN:

140246

Hom.:

Cov.:

AF XY:

0.0000146

AC XY:

AN XY:

68550

show subpopulations

Gnomad4 AFR

AF:

0.0000320

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000214

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.0000415

AC:

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

Sep 29, 2022

The c.758C>T (p.T253M) alteration is located in exon 1 (coding exon 1) of the TUBA3D gene. This alteration results from a C to T substitution at nucleotide position 758, causing the threonine (T) at amino acid position 253 to be replaced by a methionine (M). 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

-0.12

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Benign

0.71

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.54

M_CAP

Benign

0.015

MetaRNN

Benign

0.24

MetaSVM

Uncertain

-0.22

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.44

Sift4G

Uncertain

0.029

Vest4

0.51

MutPred

0.48

Gain of helix (P = 0.132);

MVP

0.41

ClinPred

0.29

GERP RS

1.3

Varity_R

0.038

gMVP

0.69

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