6-112079638-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_016262.5(TUBE1):​c.443G>A​(p.Gly148Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TUBE1
NM_016262.5 missense

Scores

12
6
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.82
Variant links:
Genes affected
TUBE1 (HGNC:20775): (tubulin epsilon 1) This gene encodes a member of the tubulin superfamily. This protein localizes to the centriolar sub-distal appendages that are associated with the older of the two centrioles after centrosome duplication. This protein plays a central role in organization of the microtubules during centriole duplication. A pseudogene of this gene is found on chromosome 5.[provided by RefSeq, Jan 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TUBE1NM_016262.5 linkc.443G>A p.Gly148Glu missense_variant Exon 6 of 12 ENST00000368662.10 NP_057346.1 Q9UJT0
TUBE1XM_047418854.1 linkc.311G>A p.Gly104Glu missense_variant Exon 5 of 11 XP_047274810.1
TUBE1XM_047418855.1 linkc.218G>A p.Gly73Glu missense_variant Exon 4 of 10 XP_047274811.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TUBE1ENST00000368662.10 linkc.443G>A p.Gly148Glu missense_variant Exon 6 of 12 1 NM_016262.5 ENSP00000357651.5 Q9UJT0

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249114
Hom.:
0
AF XY:
0.00000743
AC XY:
1
AN XY:
134656
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000547
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1459522
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
725982
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 30, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.443G>A (p.G148E) alteration is located in exon 6 (coding exon 6) of the TUBE1 gene. This alteration results from a G to A substitution at nucleotide position 443, causing the glycine (G) at amino acid position 148 to be replaced by a glutamic acid (E). 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
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.31
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.64
D
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.98
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.97
D
MetaSVM
Pathogenic
0.84
D
MutationAssessor
Pathogenic
4.0
H
PrimateAI
Pathogenic
0.86
D
PROVEAN
Pathogenic
-7.7
D
REVEL
Pathogenic
0.88
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.95
MutPred
0.88
Gain of disorder (P = 0.1433);
MVP
0.94
MPC
0.37
ClinPred
1.0
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.89
gMVP
0.94

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: rs782468172; hg19: chr6-112400841; API