chr1-235380119-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003193.5(TBCE):ā€‹c.70C>Gā€‹(p.Arg24Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R24H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

TBCE
NM_003193.5 missense

Scores

5
12
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.965
Variant links:
Genes affected
TBCE (HGNC:11582): (tubulin folding cofactor E) Cofactor E is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.858

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TBCENM_003193.5 linkc.70C>G p.Arg24Gly missense_variant Exon 2 of 17 ENST00000642610.2 NP_003184.1 Q15813-1
TBCENM_001287801.2 linkc.70C>G p.Arg24Gly missense_variant Exon 2 of 18 NP_001274730.1 Q15813-2
TBCENM_001079515.3 linkc.70C>G p.Arg24Gly missense_variant Exon 2 of 17 NP_001072983.1
TBCENM_001287802.2 linkc.-241C>G 5_prime_UTR_variant Exon 2 of 16 NP_001274731.1 Q15813A0A2R8Y6Q1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBCEENST00000642610.2 linkc.70C>G p.Arg24Gly missense_variant Exon 2 of 17 NM_003193.5 ENSP00000494796.1 Q15813-1
ENSG00000285053ENST00000645655.1 linkc.70C>G p.Arg24Gly missense_variant Exon 5 of 20 ENSP00000495202.1 Q15813-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251438
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000992
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:
6.86e-7
AC:
1
AN:
1457460
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
725114
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000385
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:
0.00
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000434
Hom.:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.070
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.77
D;D;D;D;D;.;.;D;D;D;.;.;.;.;.;.;.
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.90
.;.;.;.;.;.;.;.;.;.;D;D;T;T;D;T;D
M_CAP
Uncertain
0.17
D
MetaRNN
Pathogenic
0.86
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.76
D
MutationAssessor
Pathogenic
3.5
H;H;H;H;H;.;.;H;H;H;.;.;.;.;H;.;.
PrimateAI
Benign
0.38
T
PROVEAN
Pathogenic
-4.9
.;.;.;.;.;.;.;.;.;D;.;.;.;.;D;D;.
REVEL
Pathogenic
0.72
Sift
Uncertain
0.010
.;.;.;.;.;.;.;.;.;D;.;.;.;.;D;D;.
Sift4G
Uncertain
0.0080
.;.;.;.;.;.;.;.;.;D;.;.;.;.;D;D;.
Polyphen
1.0
D;D;D;D;D;.;.;D;D;D;.;.;.;.;.;.;.
Vest4
0.80, 0.79
MutPred
0.78
Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);Loss of methylation at R24 (P = 0.0165);
MVP
0.93
MPC
0.89
ClinPred
0.94
D
GERP RS
4.6
Varity_R
0.29
gMVP
0.93

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: rs750637765; hg19: chr1-235543434; API