Genetic Variant TUBA3D:p.Gly162Ser (chr2-131480177-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_080386.4(TUBA3D):c.484G>A(p.Gly162Ser) variant causes a missense change involving the alteration of a conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000054 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TUBA3D
NM_080386.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.48

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA3D	NM_080386.4 link	c.484G>A	p.Gly162Ser	missense_variant	Exon 4 of 5	ENST00000321253.7	NP_525125.2	P0DPH8Q1ZYQ1
MZT2A	XM_047445568.1 link	c.623-7995C>T		intron_variant	Intron 1 of 2		XP_047301524.1
MZT2A	XM_005263742.4 link	c.320-7995C>T		intron_variant	Intron 2 of 3		XP_005263799.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TUBA3D	ENST00000321253.7 link	c.484G>A	p.Gly162Ser	missense_variant	Exon 4 of 5	1	NM_080386.4	ENSP00000326042.6	P0DPH8
TUBA3D	ENST00000409047.2 link	n.310G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2
MZT2A	ENST00000427024.5 link	n.278-7995C>T		intron_variant	Intron 2 of 4	3		ENSP00000403353.1	H7C202
MZT2A	ENST00000445782.2 link	n.331-7995C>T		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

111

AN:

138538

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000960

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000820

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00148

Gnomad SAS

AF:

0.00116

Gnomad FIN

AF:

0.000833

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000702

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251360

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000542

AC:

AN:

1456502

Hom.:

Cov.:

AF XY:

0.0000608

AC XY:

AN XY:

724180

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000450

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.0000818

Gnomad4 FIN exome

AF:

0.0000380

Gnomad4 NFE exome

AF:

0.0000523

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000801

AC:

111

AN:

138648

Hom.:

Cov.:

AF XY:

0.000908

AC XY:

AN XY:

67202

show subpopulations

Gnomad4 AFR

AF:

0.000957

Gnomad4 AMR

AF:

0.000818

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00148

Gnomad4 SAS

AF:

0.00117

Gnomad4 FIN

AF:

0.000833

Gnomad4 NFE

AF:

0.000702

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00184

Hom.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Keratoconus 9

Uncertain:1

Jul 30, 2021

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.94

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.74

MetaSVM

Uncertain

-0.21

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-4.2

REVEL

Uncertain

0.37

Sift4G

Benign

0.091

Vest4

0.75

MVP

0.62

ClinPred

0.33

GERP RS

2.2

Varity_R

0.076

gMVP

0.58

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