2-219250387-C-T

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

1
10
7

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]
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]

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
TUBA4ANM_006000.3 linkc.1312G>A p.Asp438Asn missense_variant Exon 4 of 4 ENST00000248437.9 NP_005991.1 P68366-1
STK16NM_001330213.2 linkc.*1828C>T downstream_gene_variant ENST00000396738.7 NP_001317142.1 O75716

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TUBA4AENST00000248437.9 linkc.1312G>A p.Asp438Asn missense_variant Exon 4 of 4 1 NM_006000.3 ENSP00000248437.4 P68366-1
TUBA4AENST00000392088.6 linkc.1267G>A p.Asp423Asn missense_variant Exon 4 of 4 2 ENSP00000375938.2 P68366-2
STK16ENST00000396738.7 linkc.*1828C>T downstream_gene_variant 2 NM_001330213.2 ENSP00000379964.2 O75716
STK16ENST00000409638.7 linkc.*1828C>T downstream_gene_variant 1 ENSP00000386928.3 O75716

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250944
Hom.:
0
AF XY:
0.00
AC XY:
0
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:
17
AN:
1461624
Hom.:
0
Cov.:
31
AF XY:
0.0000151
AC XY:
11
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.:
32
Alfa
AF:
0.0000282
Hom.:
0
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
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
27
DANN
Uncertain
0.97
DEOGEN2
Benign
0.32
T;.
Eigen
Benign
0.14
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.076
D
MetaRNN
Uncertain
0.54
D;D
MetaSVM
Uncertain
-0.27
T
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Uncertain
0.79
T
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
D
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.

Other links and lift over

dbSNP: rs913033084; hg19: chr2-220115109; API