Genetic Variant TUBA3D:p.Ile114Asn (chr2-131479422-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

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

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

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 VariationId is 791870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080386.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA3D	NM_080386.4	MANE Select	c.341T>A	p.Ile114Asn	missense	Exon 3 of 5	NP_525125.2	P0DPH8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TUBA3D	ENST00000321253.7	TSL:1 MANE Select	c.341T>A	p.Ile114Asn	missense	Exon 3 of 5	ENSP00000326042.6	P0DPH8
TUBA3D	ENST00000409047.2	TSL:2	n.167T>A		non_coding_transcript_exon	Exon 2 of 3
MZT2A	ENST00000427024.5	TSL:3	n.278-7240A>T		intron	N/A	ENSP00000403353.1	H7C202

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

GnomAD2 exomes

AF:

0.00112

AC:

281

AN:

250172

AF XY:

0.000753

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00529

AC:

163

AN:

30792

American (AMR)

AF:

0.000247

AC:

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00000899

AC:

AN:

1111832

Other (OTH)

AF:

0.000533

AC:

AN:

60068

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.249

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00138

AC:

207

AN:

149950

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

108

AN XY:

73400

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00487

AC:

192

AN:

39390

American (AMR)

AF:

0.000725

AC:

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67996

Other (OTH)

AF:

0.00143

AC:

AN:

2100

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000877

Hom.:

ExAC

AF:

0.00487

AC:

591

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

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

PhyloP100

6.9

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

Mutation Taster

=62/38

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over