Genetic Variant TUBA4A:p.Asp438Asn (chr2-219250387-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006000.3(TUBA4A):c.1312G>A(p.Asp438Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TUBA4A
NM_006000.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.06

Variant links:

Genes affected

TUBA4A (HGNC:12407): (tubulin alpha 4a) Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. There are multiple alpha and beta tubulin genes and they are highly conserved among and between species. This gene encodes an alpha tubulin that is a highly conserved homolog of a rat testis-specific alpha tubulin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]

TUBA4A links:

STK16 (HGNC:11394): (serine/threonine kinase 16) Predicted to enable protein serine/threonine kinase activity. Involved in protein autophosphorylation. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

STK16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA4A	NM_006000.3 link	c.1312G>A	p.Asp438Asn	missense_variant	Exon 4 of 4	ENST00000248437.9	NP_005991.1	P68366-1
STK16	NM_001330213.2 link	c.*1828C>T		downstream_gene_variant		ENST00000396738.7	NP_001317142.1	O75716

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TUBA4A	ENST00000248437.9 link	c.1312G>A	p.Asp438Asn	missense_variant	Exon 4 of 4	1	NM_006000.3	ENSP00000248437.4	P68366-1
TUBA4A	ENST00000392088.6 link	c.1267G>A	p.Asp423Asn	missense_variant	Exon 4 of 4	2		ENSP00000375938.2	P68366-2
STK16	ENST00000396738.7 link	c.*1828C>T		downstream_gene_variant		2	NM_001330213.2	ENSP00000379964.2	O75716
STK16	ENST00000409638.7 link	c.*1828C>T		downstream_gene_variant		1		ENSP00000386928.3	O75716

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250944

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461624

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000117

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jul 22, 2024

Mayo Clinic Laboratories, Mayo Clinic

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BS2, PP2, PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

0.97

DEOGEN2

Benign

0.32

T;.

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.076

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-2.4

N;N

REVEL

Uncertain

0.36

Sift4G

Benign

0.061

T;T

Polyphen

0.015

B;.

Vest4

0.72

MutPred

0.21

Gain of helix (P = 0.1736);.;

MVP

0.82

MPC

1.7

ClinPred

0.81

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.68

gMVP

0.84

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