6-112086583-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016262.5(TUBE1):ā€‹c.125G>Cā€‹(p.Ser42Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

TUBE1
NM_016262.5 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27073106).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TUBE1NM_016262.5 linkuse as main transcriptc.125G>C p.Ser42Thr missense_variant 3/12 ENST00000368662.10 NP_057346.1
TUBE1XM_047418855.1 linkuse as main transcriptc.-43G>C 5_prime_UTR_variant 2/10 XP_047274811.1
TUBE1XM_047418854.1 linkuse as main transcript upstream_gene_variant XP_047274810.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TUBE1ENST00000368662.10 linkuse as main transcriptc.125G>C p.Ser42Thr missense_variant 3/121 NM_016262.5 ENSP00000357651 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250876
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135636
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000580
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1460432
Hom.:
0
Cov.:
28
AF XY:
0.00000688
AC XY:
5
AN XY:
726584
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000896
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 23, 2024The c.125G>C (p.S42T) alteration is located in exon 3 (coding exon 3) of the TUBE1 gene. This alteration results from a G to C substitution at nucleotide position 125, causing the serine (S) at amino acid position 42 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
0.19
BayesDel_addAF
Benign
-0.077
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.36
T
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-0.46
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.20
Sift
Uncertain
0.019
D
Sift4G
Benign
0.099
T
Polyphen
0.25
B
Vest4
0.33
MutPred
0.47
Gain of relative solvent accessibility (P = 0.1571);
MVP
0.73
MPC
0.094
ClinPred
0.85
D
GERP RS
4.3
Varity_R
0.28
gMVP
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs974271072; hg19: chr6-112407786; API