chr11-121045812-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001363644.2(TBCEL):ā€‹c.122C>Gā€‹(p.Ser41Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,438,132 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

TBCEL
NM_001363644.2 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79
Variant links:
Genes affected
TBCEL (HGNC:28115): (tubulin folding cofactor E like) Predicted to enable alpha-tubulin binding activity. Predicted to be involved in microtubule cytoskeleton organization; post-chaperonin tubulin folding pathway; and tubulin complex assembly. Predicted to be located in cytoskeleton. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TBCELNM_001363644.2 linkuse as main transcriptc.122C>G p.Ser41Cys missense_variant 3/9 ENST00000683345.1 NP_001350573.1
TBCEL-TECTANM_001378761.1 linkuse as main transcriptc.122C>G p.Ser41Cys missense_variant 2/30 NP_001365690.1
TBCELNM_001130047.3 linkuse as main transcriptc.122C>G p.Ser41Cys missense_variant 2/8 NP_001123519.1
TBCELNM_152715.5 linkuse as main transcriptc.122C>G p.Ser41Cys missense_variant 2/8 NP_689928.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TBCELENST00000683345.1 linkuse as main transcriptc.122C>G p.Ser41Cys missense_variant 3/9 NM_001363644.2 ENSP00000507873 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000139
AC:
2
AN:
1438132
Hom.:
0
Cov.:
30
AF XY:
0.00000280
AC XY:
2
AN XY:
715010
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000262
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:
0.0000169
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000151

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 GeneticsJun 02, 2023The c.122C>G (p.S41C) alteration is located in exon 2 (coding exon 1) of the TBCEL gene. This alteration results from a C to G substitution at nucleotide position 122, causing the serine (S) at amino acid position 41 to be replaced by a cysteine (C). 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
Uncertain
0.37
BayesDel_addAF
Uncertain
0.058
T
BayesDel_noAF
Benign
-0.15
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.070
T;T;T;T;.
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.95
.;D;D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Uncertain
0.60
D;D;D;D;D
MetaSVM
Benign
-0.74
T
MutationAssessor
Uncertain
2.9
M;.;M;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-2.3
N;D;N;D;.
REVEL
Uncertain
0.33
Sift
Uncertain
0.0010
D;D;D;D;.
Sift4G
Pathogenic
0.0
D;D;D;D;.
Polyphen
1.0
D;.;D;.;.
Vest4
0.66
MutPred
0.53
Loss of disorder (P = 0.0085);Loss of disorder (P = 0.0085);Loss of disorder (P = 0.0085);Loss of disorder (P = 0.0085);.;
MVP
0.47
MPC
1.8
ClinPred
0.93
D
GERP RS
5.6
Varity_R
0.36
gMVP
0.63

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: rs1028764515; hg19: chr11-120916521; API