Variant 2-131479422-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2

The NM_080386.4(TUBA3D):c.341T>A(p.Ile114Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00138 in 149,950 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TUBA3D
NM_080386.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.89

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 Benign. Variant got -15 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=0.013592124).

BP6

Variant 2-131479422-T-A is Benign according to our data. Variant chr2-131479422-T-A is described in ClinVar as [Benign]. Clinvar id is 791870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 207 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TUBA3D	NM_080386.4 linkuse as main transcript	c.341T>A	p.Ile114Asn	missense_variant	3/5	ENST00000321253.7	NP_525125.2
MZT2A	XM_005263742.4 linkuse as main transcript	c.320-7240A>T		intron_variant			XP_005263799.2
MZT2A	XM_047445568.1 linkuse as main transcript	c.623-7240A>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.341T>A	p.Ile114Asn	missense_variant	3/5	1	NM_080386.4	ENSP00000326042	P1
TUBA3D	ENST00000409047.2 linkuse as main transcript	n.167T>A		non_coding_transcript_exon_variant	2/3	2
MZT2A	ENST00000427024.5 linkuse as main transcript	c.279-7240A>T		intron_variant, NMD_transcript_variant		3		ENSP00000403353
MZT2A	ENST00000445782.2 linkuse as main transcript	n.331-7240A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

205

AN:

149850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000726

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:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00112

AC:

281

AN:

250172

Hom.:

AF XY:

0.000753

AC XY:

102

AN XY:

135414

show subpopulations

Gnomad AFR exome

AF:

0.0157

Gnomad AMR exome

AF:

0.000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000982

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000151

AC:

220

AN:

1458452

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

725810

show subpopulations

Gnomad4 AFR exome

AF:

0.00529

Gnomad4 AMR exome

AF:

0.000247

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.000533

GnomAD4 genome

AF:

0.00138

AC:

207

AN:

149950

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

108

AN XY:

73400

show subpopulations

Gnomad4 AFR

AF:

0.00487

Gnomad4 AMR

AF:

0.000725

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000877

Hom.:

ExAC

AF:

0.00487

AC:

591

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Benign

0.96

Eigen

Benign

-0.093

Eigen_PC

Benign

-0.087

FATHMM_MKL

Uncertain

0.79

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.43

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.42

Sift4G

Uncertain

0.022

Vest4

0.97

MVP

0.56

ClinPred

0.071

GERP RS

2.2

Varity_R

0.25

gMVP

0.83

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