Variant 2-131480409-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2PP3_ModerateBS2

The NM_080386.4(TUBA3D):c.716C>T(p.Thr239Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,588,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 30)

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: 3.26

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 -1 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.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.843

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TUBA3D	NM_080386.4 linkuse as main transcript	c.716C>T	p.Thr239Ile	missense_variant	4/5	ENST00000321253.7	NP_525125.2
MZT2A	XM_005263742.4 linkuse as main transcript	c.320-8227G>A		intron_variant			XP_005263799.2
MZT2A	XM_047445568.1 linkuse as main transcript	c.623-8227G>A		intron_variant			XP_047301524.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TUBA3D	ENST00000321253.7 linkuse as main transcript	c.716C>T	p.Thr239Ile	missense_variant	4/5	1	NM_080386.4	ENSP00000326042	P1
MZT2A	ENST00000427024.5 linkuse as main transcript	c.279-8227G>A		intron_variant, NMD_transcript_variant		3		ENSP00000403353
MZT2A	ENST00000445782.2 linkuse as main transcript	n.331-8227G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000283

AC:

AN:

141516

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000135

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:

0.000506

GnomAD3 exomes

AF:

0.0000204

AC:

AN:

245178

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

132964

show subpopulations

Gnomad AFR exome

AF:

0.000150

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

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:

1446960

Hom.:

Cov.:

AF XY:

0.00000694

AC XY:

AN XY:

720300

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000900

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000362

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.0000283

AC:

AN:

141516

Hom.:

Cov.:

AF XY:

0.0000433

AC XY:

AN XY:

69208

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000135

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.000506

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.0000751

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

May 26, 2024

The c.716C>T (p.T239I) 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 716, causing the threonine (T) at amino acid position 239 to be replaced by an isoleucine (I). 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

Benign

DANN

Benign

0.93

Eigen

Benign

-0.085

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.54

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.84

MetaSVM

Uncertain

-0.040

MutationTaster

Benign

0.94

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-4.2

REVEL

Uncertain

0.49

Sift4G

Uncertain

0.039

Vest4

0.94

MVP

0.42

ClinPred

0.41

GERP RS

-1.0

Varity_R

0.063

gMVP

0.91

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