10-5393840-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024803.3(TUBAL3):​c.1018G>A​(p.Ala340Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000255 in 1,614,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

TUBAL3
NM_024803.3 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.93
Variant links:
Genes affected
TUBAL3 (HGNC:23534): (tubulin alpha like 3) 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.027580917).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TUBAL3NM_024803.3 linkc.1018G>A p.Ala340Thr missense_variant Exon 4 of 4 ENST00000380419.8 NP_079079.1 A6NHL2-1
TUBAL3NM_001171864.2 linkc.898G>A p.Ala300Thr missense_variant Exon 4 of 4 NP_001165335.1 A6NHL2-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TUBAL3ENST00000380419.8 linkc.1018G>A p.Ala340Thr missense_variant Exon 4 of 4 1 NM_024803.3 ENSP00000369784.3 A6NHL2-1
TUBAL3ENST00000479328.1 linkc.898G>A p.Ala300Thr missense_variant Exon 4 of 4 1 ENSP00000418799.1 A6NHL2-2

Frequencies

GnomAD3 genomes
AF:
0.000355
AC:
54
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00131
Gnomad ASJ
AF:
0.00317
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000398
AC:
100
AN:
251450
Hom.:
0
AF XY:
0.000375
AC XY:
51
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000723
Gnomad ASJ exome
AF:
0.00248
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000352
Gnomad OTH exome
AF:
0.000651
GnomAD4 exome
AF:
0.000245
AC:
358
AN:
1461852
Hom.:
0
Cov.:
29
AF XY:
0.000235
AC XY:
171
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000626
Gnomad4 ASJ exome
AF:
0.00253
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000188
Gnomad4 OTH exome
AF:
0.000430
GnomAD4 genome
AF:
0.000355
AC:
54
AN:
152290
Hom.:
0
Cov.:
32
AF XY:
0.000497
AC XY:
37
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00131
Gnomad4 ASJ
AF:
0.00317
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000357
Hom.:
0
Bravo
AF:
0.000397
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000371
AC:
45
EpiCase
AF:
0.000382
EpiControl
AF:
0.000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 08, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1018G>A (p.A340T) alteration is located in exon 4 (coding exon 4) of the TUBAL3 gene. This alteration results from a G to A substitution at nucleotide position 1018, causing the alanine (A) at amino acid position 340 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.14
CADD
Benign
16
DANN
Benign
0.95
DEOGEN2
Uncertain
0.57
D;.
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.25
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.028
T;T
MetaSVM
Uncertain
-0.21
T
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-2.3
N;D
REVEL
Uncertain
0.44
Sift
Uncertain
0.010
D;D
Sift4G
Benign
0.10
T;T
Polyphen
0.64
P;P
Vest4
0.15
MVP
0.91
MPC
0.066
ClinPred
0.083
T
GERP RS
3.5
Varity_R
0.074
gMVP
0.20

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: rs139311920; hg19: chr10-5435803; API