Variant 2-131480492-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2

The NM_080386.4(TUBA3D):c.799T>A(p.Phe267Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000142 in 1,590,176 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000078 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00015 ( 9 hom. )

Consequence

TUBA3D
NM_080386.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.90

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 -2 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, 0.809

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TUBA3D	NM_080386.4 linkuse as main transcript	c.799T>A	p.Phe267Ile	missense_variant	4/5	ENST00000321253.7	NP_525125.2
MZT2A	XM_005263742.4 linkuse as main transcript	c.320-8310A>T		intron_variant			XP_005263799.2
MZT2A	XM_047445568.1 linkuse as main transcript	c.623-8310A>T		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.799T>A	p.Phe267Ile	missense_variant	4/5	1	NM_080386.4	ENSP00000326042	P1
MZT2A	ENST00000427024.5 linkuse as main transcript	c.279-8310A>T		intron_variant, NMD_transcript_variant		3		ENSP00000403353
MZT2A	ENST00000445782.2 linkuse as main transcript	n.331-8310A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000781

AC:

AN:

140818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000315

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000478

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000744

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000303

AC:

AN:

247612

Hom.:

AF XY:

0.000313

AC XY:

AN XY:

134246

show subpopulations

Gnomad AFR exome

AF:

0.0000734

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000602

Gnomad NFE exome

AF:

0.000513

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.000148

AC:

215

AN:

1449358

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

111

AN XY:

721510

show subpopulations

Gnomad4 AFR exome

AF:

0.0000344

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:

0.000769

Gnomad4 NFE exome

AF:

0.000148

Gnomad4 OTH exome

AF:

0.000150

GnomAD4 genome

AF:

0.0000781

AC:

AN:

140818

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

68834

show subpopulations

Gnomad4 AFR

AF:

0.0000315

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000478

Gnomad4 NFE

AF:

0.0000744

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000121

Hom.:

ESP6500AA

AF:

0.000239

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000496

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

Jun 07, 2024

The c.799T>A (p.F267I) alteration is located in exon 1 (coding exon 1) of the TUBA3D gene. This alteration results from a T to A substitution at nucleotide position 799, causing the phenylalanine (F) at amino acid position 267 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

Uncertain

0.036

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

0.98

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.88

M_CAP

Benign

0.061

MetaRNN

Pathogenic

0.81

MetaSVM

Pathogenic

0.88

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-4.5

REVEL

Pathogenic

0.76

Sift4G

Uncertain

0.027

Vest4

0.87

MVP

0.82

ClinPred

0.67

GERP RS

2.2

Varity_R

0.12

gMVP

0.97

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