2-219250387-C-T
Variant names:
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
NM_006000.3 missense
Scores
1
10
7
Clinical Significance
Conservation
PhyloP100: 5.06
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]
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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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TUBA4A | ENST00000248437.9 | c.1312G>A | p.Asp438Asn | missense_variant | Exon 4 of 4 | 1 | NM_006000.3 | ENSP00000248437.4 | ||
TUBA4A | ENST00000392088.6 | c.1267G>A | p.Asp423Asn | missense_variant | Exon 4 of 4 | 2 | ENSP00000375938.2 | |||
STK16 | ENST00000396738.7 | c.*1828C>T | downstream_gene_variant | 2 | NM_001330213.2 | ENSP00000379964.2 | ||||
STK16 | ENST00000409638.7 | c.*1828C>T | downstream_gene_variant | 1 | ENSP00000386928.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250944Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135598
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461624Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727092
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GnomAD4 genome Cov.: 32
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32
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N
REVEL
Uncertain
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Gain of helix (P = 0.1736);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at