chr1-235380069-CG-C
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_003193.5(TBCE):c.22delG(p.Asp8MetfsTer30) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,410 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
TBCE
NM_003193.5 frameshift
NM_003193.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.122
Publications
0 publications found
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]
TBCE Gene-Disease associations (from GenCC):
- hypoparathyroidism-retardation-dysmorphism syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P
- early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndromeInheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- encephalopathy, progressive, with amyotrophy and optic atrophyInheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, ClinGen, G2P, Ambry Genetics
- autosomal recessive Kenny-Caffey syndromeInheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 51 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-235380069-CG-C is Pathogenic according to our data. Variant chr1-235380069-CG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 2870059.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_003193.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TBCE | NM_003193.5 | MANE Select | c.22delG | p.Asp8MetfsTer30 | frameshift | Exon 2 of 17 | NP_003184.1 | Q15813-1 | |
| TBCE | NM_001287801.2 | c.22delG | p.Asp8MetfsTer30 | frameshift | Exon 2 of 18 | NP_001274730.1 | Q15813-2 | ||
| TBCE | NM_001079515.3 | c.22delG | p.Asp8MetfsTer30 | frameshift | Exon 2 of 17 | NP_001072983.1 | Q15813-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TBCE | ENST00000642610.2 | MANE Select | c.22delG | p.Asp8MetfsTer30 | frameshift | Exon 2 of 17 | ENSP00000494796.1 | Q15813-1 | |
| ENSG00000285053 | ENST00000647186.1 | c.22delG | p.Asp8MetfsTer30 | frameshift | Exon 4 of 19 | ENSP00000494775.1 | |||
| TBCE | ENST00000366601.8 | TSL:1 | c.22delG | p.Asp8MetfsTer30 | frameshift | Exon 2 of 15 | ENSP00000355560.4 | A0A2U3TZJ6 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461410Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727028 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1461410
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
727028
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33472
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26110
East Asian (EAS)
AF:
AC:
0
AN:
39670
South Asian (SAS)
AF:
AC:
0
AN:
86248
European-Finnish (FIN)
AF:
AC:
0
AN:
53390
Middle Eastern (MID)
AF:
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1111664
Other (OTH)
AF:
AC:
0
AN:
60372
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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30-35
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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