Variant 2-131480159-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4

The NM_080386.4(TUBA3D):c.466C>T(p.Arg156Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TUBA3D
NM_080386.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.10

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 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.

BP4

Computational evidence support a benign effect (MetaRNN=0.4003554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TUBA3D	NM_080386.4 linkuse as main transcript	c.466C>T	p.Arg156Trp	missense_variant	4/5	ENST00000321253.7	NP_525125.2
MZT2A	XM_005263742.4 linkuse as main transcript	c.320-7977G>A		intron_variant			XP_005263799.2
MZT2A	XM_047445568.1 linkuse as main transcript	c.623-7977G>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.466C>T	p.Arg156Trp	missense_variant	4/5	1	NM_080386.4	ENSP00000326042	P1
TUBA3D	ENST00000409047.2 linkuse as main transcript	n.292C>T		non_coding_transcript_exon_variant	3/3	2
MZT2A	ENST00000427024.5 linkuse as main transcript	c.279-7977G>A		intron_variant, NMD_transcript_variant		3		ENSP00000403353
MZT2A	ENST00000445782.2 linkuse as main transcript	n.331-7977G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

184

AN:

135284

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00218

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00152

Gnomad SAS

AF:

0.00264

Gnomad FIN

AF:

0.00118

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00136

Gnomad OTH

AF:

0.00217

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00105

AC:

1515

AN:

1439656

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

739

AN XY:

715826

show subpopulations

Gnomad4 AFR exome

AF:

0.000363

Gnomad4 AMR exome

AF:

0.000371

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000284

Gnomad4 SAS exome

AF:

0.000603

Gnomad4 FIN exome

AF:

0.000176

Gnomad4 NFE exome

AF:

0.00123

Gnomad4 OTH exome

AF:

0.000841

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00135

AC:

183

AN:

135386

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

102

AN XY:

65632

show subpopulations

Gnomad4 AFR

AF:

0.00107

Gnomad4 AMR

AF:

0.00217

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00152

Gnomad4 SAS

AF:

0.00240

Gnomad4 FIN

AF:

0.00118

Gnomad4 NFE

AF:

0.00136

Gnomad4 OTH

AF:

0.00215

Alfa

AF:

0.00371

Hom.:

ExAC

AF:

0.000997

AC:

121

EpiCase

AF:

0.000164

EpiControl

AF:

0.000713

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hepatocellular carcinoma

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Arun Kumar Laboratory, Indian Institute of Science

Jun 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.42

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.64

M_CAP

Benign

0.012

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.77

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-5.6

REVEL

Pathogenic

0.69

Sift4G

Uncertain

0.020

Vest4

0.52

MVP

0.52

ClinPred

0.066

GERP RS

1.1

Varity_R

0.16

gMVP

0.68

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