2-219271517-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001355221.1(TUBA4B):​c.544C>T​(p.Arg182Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 1,614,144 control chromosomes in the GnomAD database, including 860 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.041 ( 254 hom., cov: 32)
Exomes 𝑓: 0.017 ( 606 hom. )

Consequence

TUBA4B
NM_001355221.1 missense

Scores

2
2
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08
Variant links:
Genes affected
TUBA4B (HGNC:18637): (tubulin alpha 4b) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Predicted to be active in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0068460405).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TUBA4BNM_001355221.1 linkc.544C>T p.Arg182Cys missense_variant Exon 4 of 4 ENST00000490341.3 NP_001342150.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TUBA4BENST00000490341.3 linkc.544C>T p.Arg182Cys missense_variant Exon 4 of 4 2 NM_001355221.1 ENSP00000487719.1 Q9H853

Frequencies

GnomAD3 genomes
AF:
0.0413
AC:
6287
AN:
152146
Hom.:
251
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.104
Gnomad AMI
AF:
0.00769
Gnomad AMR
AF:
0.0153
Gnomad ASJ
AF:
0.0202
Gnomad EAS
AF:
0.101
Gnomad SAS
AF:
0.0120
Gnomad FIN
AF:
0.0168
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.0126
Gnomad OTH
AF:
0.0306
GnomAD3 exomes
AF:
0.0256
AC:
6434
AN:
251416
Hom.:
232
AF XY:
0.0236
AC XY:
3206
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.103
Gnomad AMR exome
AF:
0.00862
Gnomad ASJ exome
AF:
0.0206
Gnomad EAS exome
AF:
0.0981
Gnomad SAS exome
AF:
0.0122
Gnomad FIN exome
AF:
0.0186
Gnomad NFE exome
AF:
0.0136
Gnomad OTH exome
AF:
0.0197
GnomAD4 exome
AF:
0.0168
AC:
24539
AN:
1461880
Hom.:
606
Cov.:
68
AF XY:
0.0163
AC XY:
11846
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.106
Gnomad4 AMR exome
AF:
0.00941
Gnomad4 ASJ exome
AF:
0.0194
Gnomad4 EAS exome
AF:
0.107
Gnomad4 SAS exome
AF:
0.0121
Gnomad4 FIN exome
AF:
0.0170
Gnomad4 NFE exome
AF:
0.0112
Gnomad4 OTH exome
AF:
0.0225
GnomAD4 genome
AF:
0.0414
AC:
6308
AN:
152264
Hom.:
254
Cov.:
32
AF XY:
0.0415
AC XY:
3089
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.104
Gnomad4 AMR
AF:
0.0152
Gnomad4 ASJ
AF:
0.0202
Gnomad4 EAS
AF:
0.101
Gnomad4 SAS
AF:
0.0118
Gnomad4 FIN
AF:
0.0168
Gnomad4 NFE
AF:
0.0126
Gnomad4 OTH
AF:
0.0312
Alfa
AF:
0.0277
Hom.:
21
Bravo
AF:
0.0439
TwinsUK
AF:
0.00998
AC:
37
ALSPAC
AF:
0.0104
AC:
40
ExAC
AF:
0.0278
AC:
3378
Asia WGS
AF:
0.0560
AC:
194
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_noAF
Benign
-0.45
CADD
Benign
23
DANN
Benign
0.86
DEOGEN2
Benign
0.32
T
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Pathogenic
0.98
D
MetaRNN
Benign
0.0068
T
PrimateAI
Uncertain
0.68
T
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.85
GERP RS
2.7
Varity_R
0.089
gMVP
0.33

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: rs3731891; hg19: chr2-220136239; COSMIC: COSV67524711; API