1-235401544-AAG-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_003193.5(TBCE):c.143_144del(p.Lys48ThrfsTer2) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000479 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
TBCE
NM_003193.5 frameshift
NM_003193.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.58
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-235401544-AAG-A is Pathogenic according to our data. Variant chr1-235401544-AAG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 225483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBCE | NM_003193.5 | c.143_144del | p.Lys48ThrfsTer2 | frameshift_variant | 3/17 | ENST00000642610.2 | |
TBCE | NM_001079515.3 | c.143_144del | p.Lys48ThrfsTer2 | frameshift_variant | 3/17 | ||
TBCE | NM_001287801.2 | c.143_144del | p.Lys48ThrfsTer2 | frameshift_variant | 3/18 | ||
TBCE | NM_001287802.2 | c.-210-12888_-210-12887del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBCE | ENST00000642610.2 | c.143_144del | p.Lys48ThrfsTer2 | frameshift_variant | 3/17 | NM_003193.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251484Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135914
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461682Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 727134
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 20, 2019 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | This sequence change creates a premature translational stop signal (p.Lys48Thrfs*2) in the TBCE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TBCE are known to be pathogenic (PMID: 27666369, 34134906, 34356170). This variant is present in population databases (rs758937799, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with TBCE-related conditions. ClinVar contains an entry for this variant (Variation ID: 225483). For these reasons, this variant has been classified as Pathogenic. - |
Autosomal recessive Kenny-Caffey syndrome;C1855840:Hypoparathyroidism-retardation-dysmorphism syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at